小柯机器人

研究揭示鉴定人DPR核心启动子元件的新方法
2020-09-12 21:38

2020年9月9日,《自然》杂志在线发表了美国加州大学圣地亚哥分校James T. Kadonaga课题组的最新研究成果。他们利用机器学习鉴定了人DPR的核心启动子元件。

在本研究中,研究人员分析了人RNA聚合酶II(Pol II)的核心启动子,并利用机器学习建立了下游核心启动子区域(DPR)和TATA框生成的预测模型。研究人员研发了一种称为HARPE(随机启动子元件的高通量分析)的方法,以创建数十万个DPR(或TATA框)变体,每个变体具有已知的转录强度。

然后,研究人员通过支持向量回归(SVR)方法分析了HARPE数据,从而为序列基序提供了全面模型,并且研究人员发现基于SVR的方法可以比基于共识的方法更有效地预测转录活性。

这些结果表明,DPR是功能上重要的核心启动子元件,其广泛存在于人启动子中。值得注意的是,由于许多启动子包含一个或另一个元件,因此DPR与TATA框之间似乎存在双重性。更广泛的说该发现表明,可以通过对一系列完整序列变体进行机器学习分析来识别功能性DNA基序。

研究人员表示,Pol II核心启动子集结了促进DNA转录开始的信号,但人类中核心启动子下游元件一直未被揭示。

附:英文原文

Title: Identification of the human DPR core promoter element using machine learning

Author: Long Vo ngoc, Cassidy Yunjing Huang, California Jack Cassidy, Claudia Medrano, James T. Kadonaga

Issue&Volume: 2020-09-09

Abstract: The RNA polymerase II (Pol II) core promoter is the strategic site of convergence of the signals that lead to the initiation of DNA transcription1,2,3,4,5, but the downstream core promoter in humans has been difficult to understand1,2,3. Here we analyse the human Pol II core promoter and use machine learning to generate predictive models for the downstream core promoter region (DPR) and the TATA box. We developed a method termed HARPE (high-throughput analysis of randomized promoter elements) to create hundreds of thousands of DPR (or TATA box) variants, each with known transcriptional strength. We then analysed the HARPE data by support vector regression (SVR) to provide comprehensive models for the sequence motifs, and found that the SVR-based approach is more effective than a consensus-based method for predicting transcriptional activity. These results show that the DPR is a functionally important core promoter element that is widely used in human promoters. Notably, there appears to be a duality between the DPR and the TATA box, as many promoters contain one or the other element. More broadly, these findings show that functional DNA motifs can be identified by machine learning analysis of a comprehensive set of sequence variants.

DOI: 10.1038/s41586-020-2689-7

Source: https://www.nature.com/articles/s41586-020-2689-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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