Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Novel Diagnostic Signature of Activated NK-Associated Genes for Ulcerative Colitis: Based on Bulk and ScRNA-Seq Data

Version 1 : Received: 24 August 2023 / Approved: 28 August 2023 / Online: 29 August 2023 (09:01:01 CEST)

How to cite: Dong, S.; Zhang, Y.; Ye, L.; Cao, Q. A Novel Diagnostic Signature of Activated NK-Associated Genes for Ulcerative Colitis: Based on Bulk and ScRNA-Seq Data. Preprints 2023, 2023081902. https://doi.org/10.20944/preprints202308.1902.v1 Dong, S.; Zhang, Y.; Ye, L.; Cao, Q. A Novel Diagnostic Signature of Activated NK-Associated Genes for Ulcerative Colitis: Based on Bulk and ScRNA-Seq Data. Preprints 2023, 2023081902. https://doi.org/10.20944/preprints202308.1902.v1

Abstract

Natural killer cells are associated with the pathogenesis of ulcerative colitis (UC), but their precise contributions remain unclear. The present study sought to investigate the diagnostic value of activated NK-associated genes (ANAGs) in UC. Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, 92 differentially expressed genes (DEGs) were screened out by the “Batch correction” and “Robust rank aggregation” (RRA) methods. The immune infiltration landscape was estimated by single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT, which revealed a higher abundance of activated NK cells in noninflamed UC tissues. 54 DEGs correlated with activated NK cells were identified as ANAGs. Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were utilized to screen out 4 key ANAGs (SELP, TIMP1, MMP7, and ABCG2) and establish an activated NK-associated gene score (ANAG score). The ANAG score demonstrated excellent diagnostic value and was validated in three external datasets. The expression of the 4 key ANAGs was validated in UC patients and healthy controls (HC) samples. Through scRNA-seq data analysis, higher expression levels of SELP, TIMP1, MMP7, and ABCG2 were observed in post-capillary venules, inflammatory fibroblasts, enterocytes, and immature enterocytes. The cell scores based on the ANAGs showed enrichment in endothelial cells and fibroblasts. In conclusion, we established and validated an ANAG score with the ability to precisely diagnose UC. The 4 key ANAGs have the potential to serve as therapeutic targets in UC.

Keywords

ulcerative colitis; immune infiltration; activated NK-associated genes; diagnostic signature; bulk RNA-seq; scRNA-seq

Subject

Biology and Life Sciences, Immunology and Microbiology

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