Using regulatory variants to detect gene-gene interactions identifies networks of genes linked to cell immortalisation.,Nature Communications

当前位置： X-MOL 学术 › Nat. Commun. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Using regulatory variants to detect gene-gene interactions identifies networks of genes linked to cell immortalisation.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-17 , DOI: 10.1038/s41467-019-13762-6
D Wragg ₁ , Q Liu ₁ , Z Lin ₁ , V Riggio ₁ , C A Pugh ₁ , A J Beveridge ₂ , H Brown ₁ , D A Hume ₃ , S E Harris ₄ , I J Deary ₄ , A Tenesa ₁ , J G D Prendergast ₁

Affiliation

The extent to which the impact of regulatory genetic variants may depend on other factors, such as the expression levels of upstream transcription factors, remains poorly understood. Here we report a framework in which regulatory variants are first aggregated into sets, and using these as estimates of the total cis-genetic effects on a gene we model their non-additive interactions with the expression of other genes in the genome. Using 1220 lymphoblastoid cell lines across platforms and independent datasets we identify 74 genes where the impact of their regulatory variant-set is linked to the expression levels of networks of distal genes. We show that these networks are predominantly associated with tumourigenesis pathways, through which immortalised cells are able to rapidly proliferate. We consequently present an approach to define gene interaction networks underlying important cellular pathways such as cell immortalisation.

中文翻译：

使用调节变异检测基因-基因相互作用可识别与细胞永生化相关的基因网络。

调节性遗传变异的影响在多大程度上可能取决于其他因素，例如上游转录因子的表达水平，仍然知之甚少。在这里，我们报告了一个框架，其中首先将调节变体聚合成集合，并使用这些作为对基因的总顺式遗传效应的估计，我们模拟它们与基因组中其他基因表达的非加性相互作用。使用跨平台和独立数据集的 1220 个淋巴母细胞系，我们确定了 74 个基因，其中它们的调节变异集的影响与远端基因网络的表达水平相关联。我们表明这些网络主要与肿瘤发生途径相关，永生化细胞能够通过该途径快速增殖。

更新日期：2020-01-17

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11