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hDirect-MAP: projection-free single-cell modeling of response to checkpoint immunotherapy

文献类型：期刊论文

作者Lu, Yong5,6; Xue, Gang5; Zheng, Ningbo5; Han, Kun5; Yang, Wenzhong7; Wang, Rui-Sheng1; Wu, Lingyun8; Miller, Lance D.2; Pardee, Timothy9; Triozzi, Pierre L.9
刊名BRIEFINGS IN BIOINFORMATICS
出版日期2022-03-10
卷号23期号:2页码:16
ISSN号1467-5463
关键词single-cell RNA sequencing (scRNA-seq) single-cell mass cytometry (CyTOF) Pareto optimization projection-free single-cell modeling response to immune checkpoint blockade
DOI10.1093/bib/bbab575
英文摘要There is a lack of robust generalizable predictive biomarkers of response to immune checkpoint blockade in multiple types of cancer. We develop hDirect-MAP, an algorithm that maps T cells into a shared high-dimensional (HD) expression space of diverse T cell functional signatures in which cells group by the common T cell phenotypes rather than dimensional reduced features or a distorted view of these features. Using projection-free single-cell modeling, hDirect-MAP first removed a large group of cells that did not contribute to response and then clearly distinguished T cells into response-specific subpopulations that were defined by critical T cell functional markers of strong differential expression patterns. We found that these grouped cells cannot be distinguished by dimensional-reduction algorithms but are blended by diluted expression patterns. Moreover, these identified response-specific T cell subpopulations enabled a generalizable prediction by their HD metrics. Tested using five single-cell RNA-seq or mass cytometry datasets from basal cell carcinoma, squamous cell carcinoma and melanoma, hDirect-MAP demonstrated common response-specific T cell phenotypes that defined a generalizable and accurate predictive biomarker.
资助项目National Cancer Institute[K99CA190910] ; National Cancer Institute[4R00CA190910-03] ; Wake Forest start-up funds ; National Foundation for Cancer Research ; National Center for Advancing Translational Sciences of the National Institutes of Health[UL1TR001420] ; Endowed Hanes and Willis Family Professor in Cancer at the Wake Forest Baptist Comprehensive Cancer Center
WOS研究方向Biochemistry & Molecular Biology ; Mathematical & Computational Biology
语种英语
出版者OXFORD UNIV PRESS
WOS记录号WOS:000804196500059
源URL[http://ir.amss.ac.cn/handle/2S8OKBNM/61535]  
专题应用数学研究所
通讯作者Lu, Yong; Zhang, Wei; Jin, Guangxu
作者单位1.Harvard Med Sch, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA
2.Wake Forest Sch Med, Dept Canc Biol, 1 Med Ctr Blvd, Winston Salem, NC 27157 USA
3.Wake Forest Baptist Comprehens Canc Ctr WFBCCC, Bioinformat Shared Resource BISR, Winston Salem, NC USA
4.Wake Forest Sch Med, Ctr Precis Med, Winston Salem, NC 27101 USA
5.Wake Forest Sch Med, Dept Microbiol & Immunol, Winston Salem, NC 27101 USA
6.Houston Methodist Hosp, Canc Ctr, Weill Cornell Med, Houston, TX 77030 USA
7.Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27101 USA
8.Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China
9.Wake Forest Baptist Med Ctr, Sect Hemtol & Oncol, Dept Internal Med, Winston Salem, NC USA
10.Houston Methodist Hosp, Weill Cornell Med, Dept Pathol, Houston, TX 77030 USA
推荐引用方式
GB/T 7714		 Lu, Yong,Xue, Gang,Zheng, Ningbo,et al. hDirect-MAP: projection-free single-cell modeling of response to checkpoint immunotherapy[J]. BRIEFINGS IN BIOINFORMATICS,2022,23(2):16.
APA Lu, Yong.,Xue, Gang.,Zheng, Ningbo.,Han, Kun.,Yang, Wenzhong.,...&Jin, Guangxu.(2022).hDirect-MAP: projection-free single-cell modeling of response to checkpoint immunotherapy.BRIEFINGS IN BIOINFORMATICS,23(2),16.
MLA Lu, Yong,et al."hDirect-MAP: projection-free single-cell modeling of response to checkpoint immunotherapy".BRIEFINGS IN BIOINFORMATICS 23.2(2022):16.

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来源：数学与系统科学研究院

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