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

Yahui Long(Agency for Science, Technology and Research), Kok Siong Ang(Agency for Science, Technology and Research), Mengwei Li(Agency for Science, Technology and Research), Kian Long Kelvin Chong(Agency for Science, Technology and Research), Raman Sethi(Agency for Science, Technology and Research), Chengwei Zhong(Agency for Science, Technology and Research), Hang Xu(Agency for Science, Technology and Research), Zhiwei Ong(National Neuroscience Institute), Karishma Sachaphibulkij(National University of Singapore), Ao Chen(BGI Group (China)), Li Zeng(Duke-NUS Medical School), Huazhu Fu(Agency for Science, Technology and Research), Min Wu(Agency for Science, Technology and Research), Lina H. K. Lim(National University of Singapore), Longqi Liu(BGI Group (China)), Jinmiao Chen(National University of Singapore)
Nature Communications
March 1, 2023
Cited by 571Open Access
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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.


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