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DeepST: A versatile graph contrastive learning framework for spatially informed clustering, integration, and deconvolution of spatial transcriptomics

Yahui Long, Kok Siong Ang, Mengwei Li, Kian Long Kelvin Chong, Raman Sethi, Chengwei Zhong, Hang Xu, Zhiwei Ong, Karishma Sachaphibulkij, Ao Chen, Zeng Li, Huazhu Fu, Min Wu, Hsiu Kim Lina Lim, Longqi Liu, Jinmiao Chen
doi: https://doi.org/10.1101/2022.08.02.502407
Yahui Long
1Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648
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Kok Siong Ang
1Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648
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Mengwei Li
1Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648
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Kian Long Kelvin Chong
1Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648
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Raman Sethi
1Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648
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Chengwei Zhong
1Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648
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Hang Xu
1Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648
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Zhiwei Ong
2National Neuroscience Institute (NNI), 11 Jalan Tan Tock Seng, Singapore 308433
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Karishma Sachaphibulkij
3Immunology Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), 5 Science Drive 2, Blk MD4, Level 3, Singapore 117545
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Ao Chen
4BGI-ShenZhen, Shenzhen, China 518103
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Zeng Li
2National Neuroscience Institute (NNI), 11 Jalan Tan Tock Seng, Singapore 308433
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Huazhu Fu
5Institute of High Performance Computing (IHPC), Agency for Science, Technology and Research (A*STAR), 1 Fusionopolis Way, #16-16 Connexis, Singapore 138632
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Min Wu
6Institute for Infocomm Research, Agency for Science, Technology and Research (A*STAR), 1 Fusionopolis Way, #21-01 Connexis, Singapore 138632
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Hsiu Kim Lina Lim
3Immunology Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), 5 Science Drive 2, Blk MD4, Level 3, Singapore 117545
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Longqi Liu
4BGI-ShenZhen, Shenzhen, China 518103
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Jinmiao Chen
1Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648
3Immunology Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), 5 Science Drive 2, Blk MD4, Level 3, Singapore 117545
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  • For correspondence: chen_jinmiao@immunol.a-star.edu.sg
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Abstract

Advances in spatial transcriptomics technologies has enabled gene expression profiling of tissues while retaining the spatial context. To effectively exploit the data, spatially informed analysis tools are required. Here, we present DeepST, a versatile graph contrastive self-supervised learning framework that incorporates spatial location information and gene expression profiles to accomplish three key tasks, spatial clustering, spatial transcriptomics (ST) data integration, and single-cell RNA-seq (scRNA-seq) transfer onto ST. DeepST combines graph neural networks (GNNs) with contrastive self-supervised learning to learn spot representations in the ST data, and an auto-encoder to extract informative features in the scRNA-seq data. Spatial contrastive self-supervised learning enables the learned spatial spot representation to be more informative and discriminative by minimizing the embedding distance between spatially adjacent spots and vice versa. With DeepST, we found biologically consistent clusters with greater accuracy than competing methods. We next demonstrated DeepST’s ability to jointly analyze multiple tissue slices in both vertical and horizontal integration while correcting for batch effects. Lastly, we used DeepST to deconvolute cell types present in ST with scRNA-seq data, showing better performance than cell2location. We also demonstrated DeepST’s accurate cell type mapping to recover immune cell distribution in the different regions of breast tumor tissue. DeepST is an easily usable and computationally efficient tool for capturing and dissecting the heterogeneity within ST data, enabling biologists to gain insights into the cellular states within tissues.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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DeepST: A versatile graph contrastive learning framework for spatially informed clustering, integration, and deconvolution of spatial transcriptomics
Yahui Long, Kok Siong Ang, Mengwei Li, Kian Long Kelvin Chong, Raman Sethi, Chengwei Zhong, Hang Xu, Zhiwei Ong, Karishma Sachaphibulkij, Ao Chen, Zeng Li, Huazhu Fu, Min Wu, Hsiu Kim Lina Lim, Longqi Liu, Jinmiao Chen
bioRxiv 2022.08.02.502407; doi: https://doi.org/10.1101/2022.08.02.502407
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DeepST: A versatile graph contrastive learning framework for spatially informed clustering, integration, and deconvolution of spatial transcriptomics
Yahui Long, Kok Siong Ang, Mengwei Li, Kian Long Kelvin Chong, Raman Sethi, Chengwei Zhong, Hang Xu, Zhiwei Ong, Karishma Sachaphibulkij, Ao Chen, Zeng Li, Huazhu Fu, Min Wu, Hsiu Kim Lina Lim, Longqi Liu, Jinmiao Chen
bioRxiv 2022.08.02.502407; doi: https://doi.org/10.1101/2022.08.02.502407

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