Spatial Omics Technologies at Multimodal and Single Cell/subcellular Level

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2022 Dec 13

PMID 36514162

Authors

Jiwoon Park

Junbum Kim

Tyler Lewy

Charles M Rice

Olivier Elemento

Andre F Rendeiro

Christopher E Mason

Affiliations

Soon will be listed here.

Abstract

Spatial omics technologies enable a deeper understanding of cellular organizations and interactions within a tissue of interest. These assays can identify specific compartments or regions in a tissue with differential transcript or protein abundance, delineate their interactions, and complement other methods in defining cellular phenotypes. A variety of spatial methodologies are being developed and commercialized; however, these techniques differ in spatial resolution, multiplexing capability, scale/throughput, and coverage. Here, we review the current and prospective landscape of single cell to subcellular resolution spatial omics technologies and analysis tools to provide a comprehensive picture for both research and clinical applications.

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References

Li S, Labaj P, Zumbo P, Sykacek P, Shi W, Shi L . Detecting and correcting systematic variation in large-scale RNA sequencing data. Nat Biotechnol. 2014; 32(9):888-95. PMC: 4160374. DOI: 10.1038/nbt.3000. View

Medaglia C, Giladi A, Stoler-Barak L, De Giovanni M, Salame T, Biram A . Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq. Science. 2017; 358(6370):1622-1626. PMC: 7234837. DOI: 10.1126/science.aao4277. View

Lotstedt B, Strazar M, Xavier R, Regev A, Vickovic S . Spatial host-microbiome sequencing reveals niches in the mouse gut. Nat Biotechnol. 2023; 42(9):1394-1403. PMC: 11392810. DOI: 10.1038/s41587-023-01988-1. View

Winkler E, Kim C, Ross J, Garcia J, Gil E, Oh I . A single-cell atlas of the normal and malformed human brain vasculature. Science. 2022; 375(6584):eabi7377. PMC: 8995178. DOI: 10.1126/science.abi7377. View

Rashid R, Chen Y, Hoffer J, Muhlich J, Lin J, Krueger R . Narrative online guides for the interpretation of digital-pathology images and tissue-atlas data. Nat Biomed Eng. 2021; 6(5):515-526. PMC: 9079188. DOI: 10.1038/s41551-021-00789-8. View

He S, Bhatt R, Brown C, Brown E, Buhr D, Chantranuvatana K . High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging. Nat Biotechnol. 2022; 40(12):1794-1806. DOI: 10.1038/s41587-022-01483-z. View

Liu Y, Yang M, Deng Y, Su G, Enninful A, Guo C . High-Spatial-Resolution Multi-Omics Sequencing via Deterministic Barcoding in Tissue. Cell. 2020; 183(6):1665-1681.e18. PMC: 7736559. DOI: 10.1016/j.cell.2020.10.026. View

Bray M, Singh S, Han H, Davis C, Borgeson B, Hartland C . Cell Painting, a high-content image-based assay for morphological profiling using multiplexed fluorescent dyes. Nat Protoc. 2016; 11(9):1757-74. PMC: 5223290. DOI: 10.1038/nprot.2016.105. View

Stahl P, Salmen F, Vickovic S, Lundmark A, Fernandez Navarro J, Magnusson J . Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science. 2016; 353(6294):78-82. DOI: 10.1126/science.aaf2403. View

10.

Bai Y, Zhu B, Rovira-Clave X, Chen H, Markovic M, Chan C . Adjacent Cell Marker Lateral Spillover Compensation and Reinforcement for Multiplexed Images. Front Immunol. 2021; 12:652631. PMC: 8289709. DOI: 10.3389/fimmu.2021.652631. View

11.

Chen K, Boettiger A, Moffitt J, Wang S, Zhuang X . RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells. Science. 2015; 348(6233):aaa6090. PMC: 4662681. DOI: 10.1126/science.aaa6090. View

12.

Saarenpaa S, Shalev O, Ashkenazy H, Carlos V, Lundberg D, Weigel D . Spatial metatranscriptomics resolves host-bacteria-fungi interactomes. Nat Biotechnol. 2023; 42(9):1384-1393. PMC: 11392817. DOI: 10.1038/s41587-023-01979-2. View

13.

Kinkhabwala A, Herbel C, Pankratz J, Yushchenko D, Ruberg S, Praveen P . MACSima imaging cyclic staining (MICS) technology reveals combinatorial target pairs for CAR T cell treatment of solid tumors. Sci Rep. 2022; 12(1):1911. PMC: 8813936. DOI: 10.1038/s41598-022-05841-4. View

14.

Johnson W, Li C, Rabinovic A . Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2006; 8(1):118-27. DOI: 10.1093/biostatistics/kxj037. View

15.

Weigert M, Schmidt U, Boothe T, Muller A, Dibrov A, Jain A . Content-aware image restoration: pushing the limits of fluorescence microscopy. Nat Methods. 2018; 15(12):1090-1097. DOI: 10.1038/s41592-018-0216-7. View

16.

Radtke A, Kandov E, Lowekamp B, Speranza E, Chu C, Gola A . IBEX: A versatile multiplex optical imaging approach for deep phenotyping and spatial analysis of cells in complex tissues. Proc Natl Acad Sci U S A. 2020; 117(52):33455-33465. PMC: 7776876. DOI: 10.1073/pnas.2018488117. View

17.

Rood J, Stuart T, Ghazanfar S, Biancalani T, Fisher E, Butler A . Toward a Common Coordinate Framework for the Human Body. Cell. 2019; 179(7):1455-1467. PMC: 6934046. DOI: 10.1016/j.cell.2019.11.019. View

18.

Stoeckius M, Hafemeister C, Stephenson W, Houck-Loomis B, Chattopadhyay P, Swerdlow H . Simultaneous epitope and transcriptome measurement in single cells. Nat Methods. 2017; 14(9):865-868. PMC: 5669064. DOI: 10.1038/nmeth.4380. View

19.

Giesen C, Wang H, Schapiro D, Zivanovic N, Jacobs A, Hattendorf B . Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nat Methods. 2014; 11(4):417-22. DOI: 10.1038/nmeth.2869. View

20.

Palla G, Spitzer H, Klein M, Fischer D, Schaar A, Kuemmerle L . Squidpy: a scalable framework for spatial omics analysis. Nat Methods. 2022; 19(2):171-178. PMC: 8828470. DOI: 10.1038/s41592-021-01358-2. View