研究动态
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eaQTLdb:跨癌症类型的增强子活性数量性状位点图谱。

eaQTLdb: An atlas of enhancer activity quantitative trait loci across cancer types.

发表日期:2023 Feb 25
作者: Jiapei Yuan, Yang Tong, Xiaochuan Liu, Mulin Jun Li, Qiang Zhang, Yang Yang
来源: INTERNATIONAL JOURNAL OF CANCER

摘要:

增强元件是关键的调控元件,在包括肿瘤形成和癌症发展在内的多种生物过程中发挥着至关重要的作用。活性增强子可以产生被称为增强子RNA(eRNA)的转录本,可以用作增强子活性的指标。在这里,我们提供一个多功能的数据门户,增强子活性定量性状基因座数据库(eaQTLdb;http://www.bioailab.com:3838/eaQTLdb),用于探究基因变异对增强子活性的影响,并在不同癌症类型中优先考虑候选变异体。通过利用积累的多组学数据,我们系统地确定了不同癌症类型中影响增强子活性的遗传变异体,称为eaQTLs。我们将eaQTLs与癌症病理特征和患者整体生存相结合,以说明它们在癌症发展和进展中的潜在生物学作用。值得注意的是,我们确定了与24种不同免疫细胞类型浸润丰度相关的eaQTLs,并将其纳入eaQTLdb。此外,我们应用共定位分析来检查59种复杂疾病和特征,以确定共定位于疾病/特征GWAS信号的eaQTLs。总的来说,eaQTLdb不仅包含了在不同癌症类型中探索eaQTLs的丰富资源,而且有助于研究人员解读eaQTLs在癌症和肿瘤免疫微环境的紊乱路径中的作用,从而在精准医学中开辟新的诊断和治疗途径。本文受版权保护。版权所有。
Enhancers are key regulatory elements that exert crucial roles in diverse biological processes, including tumorigenesis and cancer development. Active enhancers could produce transcripts termed enhancer RNAs (eRNAs), which could be used as an index of enhancer activity. Here, we present a versatile data portal, enhancer activity quantitative trait loci database (eaQTLdb; http://www.bioailab.com:3838/eaQTLdb), for exploring the effects of genetic variants on enhancer activity and prioritizing candidate variants across different cancer types. By leveraging the accumulated multi-omics data, we systematically identified genetic variants which influence enhancer activity in different cancer types, termed as eaQTLs. We have linked the eaQTLs to hallmarks of cancer and patients' overall survival to illustrate their potential biological roles in cancer development and progression. Notably, eaQTLs associated with the infiltration abundance of 24 different immune cell types were identified and incorporated into eaQTLdb. In addition, we applied colocalization analyses to examine 59 complex diseases and traits to identify eaQTLs colocalized with diseases/traits GWAS signals. Overall, eaQTLdb, incorporating a rich resource for exploration of eaQTLs in different cancer types, will not only benefit users in prioritizing candidate genetic variants and enhancers, but also help researchers decipher the roles of eaQTLs in the dysregulated pathways of cancer and tumor immune microenvironment, opening new diagnostic and therapeutic avenues in precise medicine. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.