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Spatially informed clustering, integration, and deconvolution of spatial transcriptomics with GraphST

Author

Listed:
  • Yahui Long

    (Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove)

  • Kok Siong Ang

    (Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove)

  • Mengwei Li

    (Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove)

  • Kian Long Kelvin Chong

    (Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove)

  • Raman Sethi

    (Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove)

  • Chengwei Zhong

    (Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove)

  • Hang Xu

    (Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove)

  • Zhiwei Ong

    (National Neuroscience Institute)

  • Karishma Sachaphibulkij

    (National University of Singapore (NUS)
    Yong Loo Lin School of Medicine, NUS)

  • Ao Chen

    (BGI
    Jinfeng Laboratory
    BGI)

  • Li Zeng

    (National Neuroscience Institute
    DUKE-NUS Graduate Medical School)

  • Huazhu Fu

    (Agency for Science, Technology and Research (A*STAR))

  • Min Wu

    (Agency for Science, Technology and Research (A*STAR))

  • Lina Hsiu Kim Lim

    (National University of Singapore (NUS)
    Yong Loo Lin School of Medicine, NUS)

  • Longqi Liu

    (BGI)

  • Jinmiao Chen

    (Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove
    National University of Singapore (NUS))

Abstract

Spatial transcriptomics technologies generate gene expression profiles with spatial context, requiring spatially informed analysis tools for three key tasks, spatial clustering, multisample integration, and cell-type deconvolution. We present GraphST, a graph self-supervised contrastive learning method that fully exploits spatial transcriptomics data to outperform existing methods. It combines graph neural networks with self-supervised contrastive learning to learn informative and discriminative spot representations by minimizing the embedding distance between spatially adjacent spots and vice versa. We demonstrated GraphST on multiple tissue types and technology platforms. GraphST achieved 10% higher clustering accuracy and better delineated fine-grained tissue structures in brain and embryo tissues. GraphST is also the only method that can jointly analyze multiple tissue slices in vertical or horizontal integration while correcting batch effects. Lastly, GraphST demonstrated superior cell-type deconvolution to capture spatial niches like lymph node germinal centers and exhausted tumor infiltrating T cells in breast tumor tissue.

Suggested Citation

  • Yahui Long & Kok Siong Ang & Mengwei Li & Kian Long Kelvin Chong & Raman Sethi & Chengwei Zhong & Hang Xu & Zhiwei Ong & Karishma Sachaphibulkij & Ao Chen & Li Zeng & Huazhu Fu & Min Wu & Lina Hsiu Ki, 2023. "Spatially informed clustering, integration, and deconvolution of spatial transcriptomics with GraphST," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36796-3
    DOI: 10.1038/s41467-023-36796-3
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    References listed on IDEAS

    as
    1. Miranda V. Hunter & Reuben Moncada & Joshua M. Weiss & Itai Yanai & Richard M. White, 2021. "Spatially resolved transcriptomics reveals the architecture of the tumor-microenvironment interface," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
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    3. Chee-Huat Linus Eng & Michael Lawson & Qian Zhu & Ruben Dries & Noushin Koulena & Yodai Takei & Jina Yun & Christopher Cronin & Christoph Karp & Guo-Cheng Yuan & Long Cai, 2019. "Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH+," Nature, Nature, vol. 568(7751), pages 235-239, April.
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    Cited by:

    1. Duy Pham & Xiao Tan & Brad Balderson & Jun Xu & Laura F. Grice & Sohye Yoon & Emily F. Willis & Minh Tran & Pui Yeng Lam & Arti Raghubar & Priyakshi Kalita-de Croft & Sunil Lakhani & Jana Vukovic & Ma, 2023. "Robust mapping of spatiotemporal trajectories and cell–cell interactions in healthy and diseased tissues," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
    2. Antonio Agostini & Geny Piro & Frediano Inzani & Giuseppe Quero & Annachiara Esposito & Alessia Caggiano & Lorenzo Priori & Alberto Larghi & Sergio Alfieri & Raffaella Casolino & Giulia Scaglione & Vi, 2024. "Identification of spatially-resolved markers of malignant transformation in Intraductal Papillary Mucinous Neoplasms," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Tianci Song & Charles Broadbent & Rui Kuang, 2023. "GNTD: reconstructing spatial transcriptomes with graph-guided neural tensor decomposition informed by spatial and functional relations," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Chen-Rui Xia & Zhi-Jie Cao & Xin-Ming Tu & Ge Gao, 2023. "Spatial-linked alignment tool (SLAT) for aligning heterogenous slices," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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