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Article ; Online: Identification of antigen-presentation related B cells as a key player in Crohn's disease using single-cell dissecting, hdWGCNA, and deep learning.

Shen, Xin / Mo, Shaocong / Zeng, Xinlei / Wang, Yulin / Lin, Lingxi / Weng, Meilin / Sugasawa, Takehito / Wang, Lei / Gu, Wenchao / Nakajima, Takahito

Clinical and experimental medicine

2023  Volume 23, Issue 8, Page(s) 5255–5267

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 ...

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.
MeSH term(s) Humans ; Crohn Disease/diagnosis ; Crohn Disease/pathology ; Antigen Presentation ; Deep Learning ; Intestinal Mucosa/pathology ; B-Lymphocytes
Language English
Publishing date 2023-08-08
Publishing country Italy
Document type Journal Article
ZDB-ID 2053018-3
ISSN 1591-9528 ; 1591-8890
ISSN (online) 1591-9528
ISSN 1591-8890
DOI 10.1007/s10238-023-01145-7
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