Uncovering the spatial landscape of molecular interactions within the tumor microenvironment through latent spaces

被引：13

作者：

Deshpande, Atul ^{[1
,2
,3
]}

Loth, Melanie ^{[1
,2
,3
]}

Sidiropoulos, Dimitrios N. ^{[1
,2
,3
,4
]}

Zhang, Shuming ^{[5
]}

Yuan, Long ^{[3
,6
]}

Bell, Alexander T. F. ^{[1
,2
,3
]}

Zhu, Qingfeng ^{[1
,2
,3
]}

Ho, Won Jin ^{[1
,2
,3
]}

Santa-Maria, Cesar ^{[1
]}

Gilkes, Daniele M.

Williams, Stephen R. ^{[7
]}

Uytingco, Cedric R. ^{[7
]}

Chew, Jennifer ^{[7
]}

Hartnett, Andrej

Bent, Zachary W.

Favorov, Alexander V. ^{[1
,2
,3
]}

Popel, Aleksander S. ^{[1
,5
]}

Yarchoan, Mark ^{[1
,2
,3
]}

Kiemen, Ashley ^{[1
,8
]}

Wu, Pei-Hsun ^{[9
]}

Fujikura, Kohei

Wirtz, Denis ^{[1
,2
,3
,8
,9
,10
]}

Wood, Laura D. ^{[1
,8
,11
]}

Zheng, Lei ^{[1
,3
]}

Jaffee, Elizabeth M. ^{[1
,2
,3
]}

Anders, Robert A. ^{[3
,8
]}

Danilova, Ludmila ^{[1
,2
,3
]}

Stein-O'Brien, Genevieve ^{[1
,2
,3
]}

Kagohara, Luciane T. ^{[1
,2
,3
]}

Fertig, Elana J. ^{[1
,2
,3
,5
,12
]}

机构：

[1] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Dept Oncol, Baltimore, MD 21218 USA

[2] Johns Hopkins Univ, Convergence Inst, Baltimore, MD 21218 USA

[3] Johns Hopkins Univ, Bloomberg Kimmel Inst Canc Immunotherapy, Sch Med, Baltimore, MD 21218 USA

[4] Johns Hopkins Univ, Sch Med, Cellular & Mol Med, Baltimore, MD USA

[5] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21218 USA

[6] Johns Hopkins Univ, Sch Med, Dept Immunol, Baltimore, MD USA

[7] 10x Genom Inc, Pleasanton, CA USA

[8] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD USA

[9] Johns Hopkins Univ, Whiting Sch Engn, Dept Chem & Biomol Engn, Baltimore, MD USA

[10] Johns Hopkins Univ, Johns Hopkins Phys Sci Oncol Ctr, Inst NanoBioTechnol, Baltimore, MD USA

[11] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD USA

[12] Johns Hopkins Univ, Whiting Sch Engn, Dept Appl Math & Stat, Baltimore, MD 21218 USA

来源：

CELL SYSTEMS | 2023年 / 14卷 / 04期

关键词：

SINGLE-CELL;

D O I：

10.1016/j.cels.2023.03.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Recent advances in spatial transcriptomics (STs) enable gene expression measurements from a tissue sam-ple while retaining its spatial context. This technology enables unprecedented in situ resolution of the regu-latory pathways that underlie the heterogeneity in the tumor as well as the tumor microenvironment (TME). The direct characterization of cellular co-localization with spatial technologies facilities quantification of the molecular changes resulting from direct cell-cell interaction, as it occurs in tumor-immune interactions. We present SpaceMarkers, a bioinformatics algorithm to infer molecular changes from cell-cell interactions from latent space analysis of ST data. We apply this approach to infer the molecular changes from tumor -im-mune interactions in Visium spatial transcriptomics data of metastasis, invasive and precursor lesions, and immunotherapy treatment. Further transfer learning in matched scRNA-seq data enabled further quantifica-tion of the specific cell types in which SpaceMarkers are enriched. Altogether, SpaceMarkers can identify the location and context-specific molecular interactions within the TME from ST data.

引用

页码：285 / +

页数：22

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