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

整合白色念珠菌诱导的单细胞基因表达数据和分泌蛋白浓度,揭示炎症的遗传调控因子

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Abstract

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.

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