eQTLs 确定了个体对败血症反应的调控网络和变异驱动因素。

IF 11.1 Q1 CELL BIOLOGY
Cell genomics Pub Date : 2024-07-10 Epub Date: 2024-06-18 DOI:10.1016/j.xgen.2024.100587
Katie L Burnham, Nikhil Milind, Wanseon Lee, Andrew J Kwok, Kiki Cano-Gamez, Yuxin Mi, Cyndi G Geoghegan, Ping Zhang, Stuart McKechnie, Nicole Soranzo, Charles J Hinds, Julian C Knight, Emma E Davenport
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引用次数: 0

摘要

败血症是一种由感染反应失调引起的危及生命的器官功能障碍临床综合征,其疾病异质性是开发靶向治疗的主要障碍。我们之前已经确定了基于基因表达的患者亚群(脓毒症反应特征 [SRS]),这些亚群对预后和潜在的病理生理学具有参考价值。在此,我们旨在研究基因变异在决定宿主转录组反应中的作用,并勾勒出 SRS 的基础调控网络。利用对 638 名成年败血症患者的基因分型和 RNA 测序数据,我们报告了这种疾病背景下的 16,049 个独立表达(eQTLs)和 32 个共表达模块(modQTLs)定量性状位点。我们确定了 1,578 个 SNP 基因对的 SRS 与基因型之间的显着交互作用,并结合转录因子 (TF) 结合位点信息(SNP2TFBS)和预测调控子活性(DoRothEA)确定了候选上游调控因子。总之,这些方法确定了宿主遗传变异、细胞亚型和个体转录组对感染的反应之间的潜在机理联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
eQTLs identify regulatory networks and drivers of variation in the individual response to sepsis.

Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection, for which disease heterogeneity is a major obstacle to developing targeted treatments. We have previously identified gene-expression-based patient subgroups (sepsis response signatures [SRS]) informative for outcome and underlying pathophysiology. Here, we aimed to investigate the role of genetic variation in determining the host transcriptomic response and to delineate regulatory networks underlying SRS. Using genotyping and RNA-sequencing data on 638 adult sepsis patients, we report 16,049 independent expression (eQTLs) and 32 co-expression module (modQTLs) quantitative trait loci in this disease context. We identified significant interactions between SRS and genotype for 1,578 SNP-gene pairs and combined transcription factor (TF) binding site information (SNP2TFBS) and predicted regulon activity (DoRothEA) to identify candidate upstream regulators. Overall, these approaches identified putative mechanistic links between host genetic variation, cell subtypes, and the individual transcriptomic response to infection.

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CiteScore
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