UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing

doi:10.1038/s41592-024-02586-y

	UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing
	Li, Yun 1,2,3; Huang, Zheng 1,2,3; Xu, Lubin 4; Fan, Yanling 1,2; Ping, Jun 5; Li, Guochao 1,2; Chen, Yanjie 1,2,3,6; Yu, Chengwei 1,2,3,7; Wang, Qifei 1,2,3; Song, Turun 8,9; Lin, Tao 8,9; Liu, Mengmeng 1,2,3; Xu, Yangqing 1,2,3; Ai, Na 1,2,3; Meng, Xini 1,2,3; Qiao, Qin 1,2; Ji, Hongbin3,10,11,12 ; Qin, Zhen 10; Jin, Shuo 13,14; Jiang, Nan 13,14; Wang, Minxian 1,2,3; Shu, Shaokun 15; Zhang, Feng 5; Zhang, Weiqi 1,2,3; Liu, Guang-Hui 3,16,17,18,19,20,21,22; Chen, Limeng 4; Jiang, Lan 1,2,3,6,7
	2025
发表期刊	NATURE METHODS (IF:36.1[JCR-2023],45.6[5-Year])
ISSN	1548-7091
EISSN	1548-7105
发表状态	已发表
DOI	10.1038/s41592-024-02586-y
摘要	The use of single-cell combinatorial indexing sequencing via droplet microfluidics presents an attractive approach for balancing cost, scalability, robustness and accessibility. However, existing methods often require tailored protocols for individual modalities, limiting their automation potential and clinical applicability. To address this, we introduce UDA-seq, a universal workflow that integrates a post-indexing step to enhance throughput and systematically adapt existing droplet-based single-cell multimodal methods. UDA-seq was benchmarked across various tissue and cell types, enabling several common multimodal analyses, including single-cell co-assay of RNA and VDJ, RNA and chromatin, and RNA and CRISPR perturbation. Notably, UDA-seq facilitated the efficient generation of over 100,000 high-quality single-cell datasets from three dozen frozen clinical biopsy specimens within a single-channel droplet microfluidics experiment. Downstream analysis demonstrated the robustness of this approach in identifying rare cell subpopulations associated with clinical phenotypes and exploring the vulnerability of cancer cells.
URL	查看原文
收录类别	SCI
语种	英语
资助项目	the National Key Research and Development Program of China (grant no. 2019YFA0801702) the Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XDB38020500) National Key Research and Development Program of China (grant no. 2023Y[
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemical Research Methods
WOS记录号	WOS:001400817500001
出版者	NATURE PORTFOLIO
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/483920
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_季红斌组
通讯作者	Shu, Shaokun; Zhang, Feng; Zhang, Weiqi; Liu, Guang-Hui; Chen, Limeng; Jiang, Lan
作者单位	1.China Natl Ctr Bioinformat, Beijing, Peoples R China 2.Chinese Acad Sci, Beijing Inst Genom, Beijing, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Peking Union Med Coll, Dept Nephrol, Beijing, Peoples R China 5.Wenzhou Med Univ, Joint Innovat Ctr Engn Med, Quzhou Affiliated Hosp, Quzhou 324000, Peoples R China 6.Univ Chinese Acad Sci, Sino Danish Coll, Beijing, Peoples R China 7.Univ Chinese Acad Sci, Coll Future Technol Coll, Beijing, Peoples R China 8.Sichuan Univ, West China Hosp, Inst Urol, Dept Urol, Chengdu, Peoples R China 9.Sichuan Univ, West China Hosp, Kidney Transplantat Ctr, Chengdu, Peoples R China 10.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci, Key Lab Multicell Syst, Shanghai, Peoples R China 11.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 12.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Hangzhou, Peoples R China 13.Tsinghua Univ, Beijing Tsinghua Changgung Hosp, Sch Clin Med, Hepatopancreato biliary Ctr, Beijing, Peoples R China 14.Chinese Acad Med Sci, Res Unit Precis Hepatobiliary Surg Paradigm, Beijing, Peoples R China 15.Peking Univ, Canc Hosp & Inst, Int Canc Inst, Yunnan Baiyao Int Med Res Ctr,State Key Lab Mol On, Beijing, Peoples R China 16.Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing, Peoples R China 17.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China 18.Beijing Inst Stem Cell & Regenerat Med, Beijing, Peoples R China 19.Capital Med Univ, Xuanwu Hosp, Adv Innovat Ctr Human Brain Protect, Beijing, Peoples R China 20.Capital Med Univ, Xuanwu Hosp, Natl Clin Res Ctr Geriatr Disorders, Beijing, Peoples R China 21.Capital Med Univ, Xuanwu Hosp, Aging Translat Med Ctr, Beijing Municipal Geriatr Med Res Ctr,Int Ctr Agin, Beijing, Peoples R China 22.Aging Biomarker Consortium, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Li, Yun,Huang, Zheng,Xu, Lubin,et al. UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing[J]. NATURE METHODS,2025.
APA	Li, Yun.,Huang, Zheng.,Xu, Lubin.,Fan, Yanling.,Ping, Jun.,...&Jiang, Lan.(2025).UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing.NATURE METHODS.
MLA	Li, Yun,et al."UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing".NATURE METHODS (2025).