1. Identification of antigen-presentation related B cells as a key player in Crohn's disease using single-cell dissecting, hdWGCNA, and deep learning.
- Author
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Shen, Xin, Mo, Shaocong, Zeng, Xinlei, Wang, Yulin, Lin, Lingxi, Weng, Meilin, Sugasawa, Takehito, Wang, Lei, Gu, Wenchao, and Nakajima, Takahito
- Subjects
CROHN'S disease ,B cells ,CONVOLUTIONAL neural networks ,DEEP learning ,ANTIGEN presentation - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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