Spatial transcriptomics at subspot resolution with BayesSpace

被引:455
作者
Zhao, Edward [1 ,2 ]
Stone, Matthew R. [3 ]
Ren, Xing [1 ]
Guenthoer, Jamie [4 ]
Smythe, Kimberly S. [5 ]
Pulliam, Thomas [6 ]
Williams, Stephen R. [7 ]
Uytingco, Cedric R. [7 ]
Taylor, Sarah E. B. [7 ]
Nghiem, Paul [5 ,6 ,8 ]
Bielas, Jason H. [3 ,9 ,10 ]
Gottardo, Raphael [1 ,2 ]
机构
[1] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA
[2] Univ Washington, Dept Biostat, Seattle, WA 98195 USA
[3] Fred Hutchinson Canc Res Ctr, Fred Hutch Innovat Lab, Immunotherapy Integrated Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA
[4] Fred Hutchinson Canc Res Ctr, Human Biol Div, 1124 Columbia St, Seattle, WA 98104 USA
[5] Fred Hutchinson Canc Res Ctr, Clin Res Div, 1124 Columbia St, Seattle, WA 98104 USA
[6] Univ Washington, Dept Med, Div Dermatol, Seattle, WA USA
[7] 10x Genom, Pleasanton, CA USA
[8] Seattle Canc Care Alliance, Seattle, WA USA
[9] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Translat Res Program, 1124 Columbia St, Seattle, WA 98104 USA
[10] Univ Washington, Dept Pathol, Seattle, WA 98195 USA
基金
美国国家卫生研究院;
关键词
CARCINOMA IN-SITU; SINGLE-CELL; BREAST-CANCER; GENE-EXPRESSION; PROTEIN-KINASE; SEQ; VISUALIZATION; PROGRESSION; GROWTH;
D O I
10.1038/s41587-021-00935-2
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
BayesSpace increases the resolution of spatial transcriptomics by using neighborhood information. Recent spatial gene expression technologies enable comprehensive measurement of transcriptomic profiles while retaining spatial context. However, existing analysis methods do not address the limited resolution of the technology or use the spatial information efficiently. Here, we introduce BayesSpace, a fully Bayesian statistical method that uses the information from spatial neighborhoods for resolution enhancement of spatial transcriptomic data and for clustering analysis. We benchmark BayesSpace against current methods for spatial and non-spatial clustering and show that it improves identification of distinct intra-tissue transcriptional profiles from samples of the brain, melanoma, invasive ductal carcinoma and ovarian adenocarcinoma. Using immunohistochemistry and an in silico dataset constructed from scRNA-seq data, we show that BayesSpace resolves tissue structure that is not detectable at the original resolution and identifies transcriptional heterogeneity inaccessible to histological analysis. Our results illustrate BayesSpace's utility in facilitating the discovery of biological insights from spatial transcriptomic datasets.
引用
收藏
页码:1375 / +
页数:14
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