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Identification of antigen-presentation related B cells as a key player in Crohn’s disease using single-cell dissecting, hdWGCNA, and deep learning

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Abstract

Crohn’s disease (CD) arises from intricate intercellular interactions within the intestinal lamina propria. Our objective was to use single-cell RNA sequencing to investigate CD pathogenesis and explore its clinical significance. We identified a distinct subset of B cells, highly infiltrated in the CD lamina propria, that expressed genes related to antigen presentation. Using high-dimensional weighted gene co-expression network analysis and nine machine learning techniques, we demonstrated that the antigen-presenting CD-specific B cell signature effectively differentiated diseased mucosa from normal mucosa (Independent external testing AUC = 0.963). Additionally, using MCPcounter and non-negative matrix factorization, we established a relationship between the antigen-presenting CD-specific B cell signature and immune cell infiltration and patient heterogeneity. Finally, we developed a gene-immune convolutional neural network deep learning model that accurately diagnosed CD mucosa in diverse cohorts (Independent external testing AUC = 0.963). Our research has revealed a population of B cells with a potential promoting role in CD pathogenesis and represents a fundamental step in the development of future clinical diagnostic tools for the disease.

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Acknowledgements

We are grateful to all the members of the Bioinfo_composer team, which is the foremost bioinformatics platform in China, for their altruistic assistance.

Funding

This work was supported by JSPS KAKENHI Grant Number JP22K20814.

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XS analyzed the data and presented the results, SCM and WCG designed the research. XLZ wrote the introduction and discussion of the manuscript. YLW and LW modified the manuscript to the submission format. LXL and MLW assisted with the literature search. TS and TN provided suggestions on data analysis.

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Correspondence to Shaocong Mo or Wenchao Gu.

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Shen, X., Mo, S., Zeng, X. et al. Identification of antigen-presentation related B cells as a key player in Crohn’s disease using single-cell dissecting, hdWGCNA, and deep learning. Clin Exp Med 23, 5255–5267 (2023). https://doi.org/10.1007/s10238-023-01145-7

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