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Simultaneous Profiling of Host Expression and Microbial Abundance by Spatial Meta-Transcriptome Sequencing

View ORCID ProfileLin Lyu, Xue Li, Ru Feng, Xin Zhou, Tuhin K. Guha, Xiaofei Yu, Guo Qiang Chen, Yufeng Yao, Bing Su, Duowu Zou, Michael P. Snyder, View ORCID ProfileLei Chen
doi: https://doi.org/10.1101/2022.08.04.502882
Lin Lyu
1Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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  • ORCID record for Lin Lyu
Xue Li
1Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Ru Feng
1Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Xin Zhou
2Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305, USA
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Tuhin K. Guha
2Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305, USA
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Xiaofei Yu
3State Key Laboratory of Genetic Engineering, School of Life Sciences, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, 20082, China
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Guo Qiang Chen
4Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, State Key Laboratory of Oncogenes and Related Genes and Chinese Academy of Medical Sciences, Shanghai Cancer Institute, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China
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Yufeng Yao
5Laboratory of Bacterial Pathogenesis, Department of Microbiology and Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China
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Bing Su
1Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Duowu Zou
6Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
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  • For correspondence: lei.chen@sjtu.edu.cn mpsnyder@stanford.edu zdw_pi@163.com
Michael P. Snyder
2Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305, USA
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  • For correspondence: lei.chen@sjtu.edu.cn mpsnyder@stanford.edu zdw_pi@163.com
Lei Chen
1Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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  • ORCID record for Lei Chen
  • For correspondence: lei.chen@sjtu.edu.cn mpsnyder@stanford.edu zdw_pi@163.com
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Abstract

We developed an analysis pipeline that can extract microbial sequences from Spatial Transcriptomic (ST) data and assign taxonomic labels, generating a spatial microbial abundance matrix in addition to the default host expression matrix, enabling simultaneous analysis of host expression and microbial distribution. We called the pipeline Spatial Meta-transcriptome (SMT) and applied it on both human and murine intestinal sections and validated the spatial microbial abundance information with alternative assays. Biological insights were gained from this novel data that demonstrated host-microbe interaction at various spatial scales. Finally, we tested experimental modification that can increase microbial capture while preserving host spatial expression quality, and by use of positive controls, quantitatively demonstrated the capture efficiency and recall of our methods. This proof of concept work demonstrates the feasibility of Spatial Meta-transcriptomic analysis, and paves the way for further experimental optimization and application.

Competing Interest Statement

The authors have declared no competing interest.

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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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Posted August 05, 2022.
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Simultaneous Profiling of Host Expression and Microbial Abundance by Spatial Meta-Transcriptome Sequencing
Lin Lyu, Xue Li, Ru Feng, Xin Zhou, Tuhin K. Guha, Xiaofei Yu, Guo Qiang Chen, Yufeng Yao, Bing Su, Duowu Zou, Michael P. Snyder, Lei Chen
bioRxiv 2022.08.04.502882; doi: https://doi.org/10.1101/2022.08.04.502882
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Simultaneous Profiling of Host Expression and Microbial Abundance by Spatial Meta-Transcriptome Sequencing
Lin Lyu, Xue Li, Ru Feng, Xin Zhou, Tuhin K. Guha, Xiaofei Yu, Guo Qiang Chen, Yufeng Yao, Bing Su, Duowu Zou, Michael P. Snyder, Lei Chen
bioRxiv 2022.08.04.502882; doi: https://doi.org/10.1101/2022.08.04.502882

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