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      Deciphering spatial domains from spatially resolved transcriptomics with an adaptive graph attention auto-encoder

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          Abstract

          Recent advances in spatially resolved transcriptomics have enabled comprehensive measurements of gene expression patterns while retaining the spatial context of the tissue microenvironment. Deciphering the spatial context of spots in a tissue needs to use their spatial information carefully. To this end, we develop a graph attention auto-encoder framework STAGATE to accurately identify spatial domains by learning low-dimensional latent embeddings via integrating spatial information and gene expression profiles. To better characterize the spatial similarity at the boundary of spatial domains, STAGATE adopts an attention mechanism to adaptively learn the similarity of neighboring spots, and an optional cell type-aware module through integrating the pre-clustering of gene expressions. We validate STAGATE on diverse spatial transcriptomics datasets generated by different platforms with different spatial resolutions. STAGATE could substantially improve the identification accuracy of spatial domains, and denoise the data while preserving spatial expression patterns. Importantly, STAGATE could be extended to multiple consecutive sections to reduce batch effects between sections and extracting three-dimensional (3D) expression domains from the reconstructed 3D tissue effectively.

          Abstract

          Breakthrough technologies for spatially resolved transcriptomics have enabled genome-wide profiling of gene expressions in captured locations. Here the authors integrate gene expressions and spatial locations to identify spatial domains using an adaptive graph attention auto-encoder.

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          Most cited references41

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          Fast unfolding of communities in large networks

          Journal of Statistical Mechanics: Theory and Experiment, 2008(10), P10008
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            SCANPY : large-scale single-cell gene expression data analysis

            Scanpy is a scalable toolkit for analyzing single-cell gene expression data. It includes methods for preprocessing, visualization, clustering, pseudotime and trajectory inference, differential expression testing, and simulation of gene regulatory networks. Its Python-based implementation efficiently deals with data sets of more than one million cells (https://github.com/theislab/Scanpy). Along with Scanpy, we present AnnData, a generic class for handling annotated data matrices (https://github.com/theislab/anndata).
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              UMAP: Uniform Manifold Approximation and Projection

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                Author and article information

                Contributors
                zsh@amss.ac.cn
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                1 April 2022
                1 April 2022
                2022
                : 13
                : 1739
                Affiliations
                [1 ]GRID grid.9227.e, ISNI 0000000119573309, NCMIS, CEMS, RCSDS, Academy of Mathematics and Systems Science, , Chinese Academy of Sciences, ; Beijing, 100190 China
                [2 ]GRID grid.410726.6, ISNI 0000 0004 1797 8419, School of Mathematical Sciences, , University of Chinese Academy of Sciences, ; Beijing, 100049 China
                [3 ]GRID grid.9227.e, ISNI 0000000119573309, Center for Excellence in Animal Evolution and Genetics, , Chinese Academy of Sciences, ; Kunming, 650223 China
                [4 ]GRID grid.410726.6, ISNI 0000 0004 1797 8419, Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, , University of Chinese Academy of Sciences, Chinese Academy of Sciences, ; Hangzhou, 310024 China
                Author information
                http://orcid.org/0000-0003-0192-7118
                Article
                29439
                10.1038/s41467-022-29439-6
                8976049
                35365632
                40704e1a-aeb5-499b-a3e6-6118bde78f80
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 7 October 2021
                : 16 March 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 61621003
                Award Recipient :
                Funded by: the National Key Research and Development Program of China [No. 2019YFA0709501 to S.Z.], the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) [Nos. XDA16021400, XDPB17 to S.Z.], the Key-Area Research and Development of Guangdong Province [No. 2020B1111190001 to S.Z.], the National Natural Science Foundation of China [Nos. 12126605, 61621003 to S.Z.], the National Ten Thousand Talent Program for Young Top-notch Talents, and the CAS Frontier Science Research Key Project for Top Young Scientist [No. QYZDB-SSW-SYS008 to S.Z.].
                Categories
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                © The Author(s) 2022

                Uncategorized
                computational models,data mining,functional clustering,software,classification and taxonomy

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