Integration of Candida albicans -induced single-cell gene expression data and secretory protein concentrations reveal genetic regulators of inflammation.

Autor:	Boahen CK; Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands.; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, Netherlands., Oelen R; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., Le K; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., Netea MG; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, Netherlands.; Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany., Franke L; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., van der Wijst MGP; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., Kumar V; Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands.; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, Netherlands.; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.; Nitte University Centre for Science Education and Research (NUCSER), Nitte (Deemed to be University), Mangalore, India.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Feb 14; Vol. 14, pp. 1069379. Date of Electronic Publication: 2023 Feb 14 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1069379
Abstrakt:	Both gene expression and protein concentrations are regulated by genetic variants. Exploring the regulation of both eQTLs and pQTLs simultaneously in a context- and cell-type dependent manner may help to unravel mechanistic basis for genetic regulation of pQTLs. Here, we performed meta-analysis of Candida albicans -induced pQTLs from two population-based cohorts and intersected the results with Candida -induced cell-type specific expression association data (eQTL). This revealed systematic differences between the pQTLs and eQTL, where only 35% of the pQTLs significantly correlated with mRNA expressions at single cell level, indicating the limitation of eQTLs use as a proxy for pQTLs. By taking advantage of the tightly co-regulated pattern of the proteins, we also identified SNPs affecting protein network upon Candida stimulations. Colocalization of pQTLs and eQTLs signals implicated several genomic loci including MMP-1 and AMZ1. Analysis of Candida -induced single cell gene expression data implicated specific cell types that exhibit significant expression QTLs upon stimulation. By highlighting the role of trans-regulatory networks in determining the abundance of secretory proteins, our study serve as a framework to gain insights into the mechanisms of genetic regulation of protein levels in a context-dependent manner. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Boahen, Oelen, Le, Netea, Franke, Wijst and Kumar.)
Databáze:	MEDLINE
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