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

Date:	19 April 2023
PMID:	PMC10236356
Category:	N/A
Authors:	Atul Deshpande, Melanie Loth, Dimitrios N Sidiropoulos, Shuming Zhang, Long Yuan, Alexander T F Bell, Qingfeng Zhu, Won Jin Ho, Cesar Santa-Maria, Daniele M Gilkes, Stephen R Williams, Cedric R Uytingco, Jennifer Chew, Andrej Hartnett, Zachary W Bent, Alexander V Favorov, Aleksander S Popel, Mark Yarchoan, Ashley Kiemen, Pei-Hsun Wu, Kohei Fujikura, Denis Wirtz, Laura D Wood, Lei Zheng, Elizabeth M Jaffee, Robert A Anders, Ludmila Danilova, Genevieve Stein-O'Brien, Luciane T Kagohara, Elana J Fertig
Abstract:

Recent advances in spatial transcriptomics (STs) enable gene expression measurements from a tissue sample while retaining its spatial context. This technology enables unprecedented in situ resolution of the regulatory 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-immune 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 quantification 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.

---

Acknowledgements:

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, or the National Institute of Health.

The Translational and Basic Science Research in Early Lesions (TBEL) Research Consortia is supported and funded by grants from the National Cancer Institute and the National Institutes of Health under the following award numbers:

Project Number:	Awardee Organization
U54CA274374	Fred Hutchinson Cancer Center
U54CA274375	Houston Methodist Research Institute
U54CA274370	Johns Hopkins University
U54CA274371	UT MD Anderson Cancer Center
U54CA274367	Vanderbilt University Medical Center