Modeling gene regulation from paired expression and chromatin accessibility data

doi:10.1073/pnas.1704553114

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	Modeling gene regulation from paired expression and chromatin accessibility data
	Duren, Zhana 1,2,3; Chen, Xi 2; Jiang, Rui 3,4,5; Wang, Yong1 ; Wong, Wing Hung 2
	2017-06-20
发表期刊	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN	0027-8424
卷号	114 期号:25 页码:E4914-E4923
摘要	The rapid increase of genome-wide datasets on gene expression, chromatin states, and transcription factor (TF) binding locations offers an exciting opportunity to interpret the information encoded in genomes and epigenomes. This task can be challenging as it requires joint modeling of context-specific activation of cis-regulatory elements (REs) and the effects on transcription of associated regulatory factors. To meet this challenge, we propose a statistical approach based on paired expression and chromatin accessibility (PECA) data across diverse cellular contexts. In our approach, we model (i) the localization to REs of chromatin regulators (CRs) based on their interaction with sequence-specific TFs, (ii) the activation of REs due to CRs that are localized to them, and (iii) the effect of TFs bound to activated REs on the transcription of target genes (TGs). The transcriptional regulatory network inferred by PECA provides a detailed view of how trans-and cis-regulatory elements work together to affect gene expression in a context-specific manner. We illustrate the feasibility of this approach by analyzing paired expression and accessibility data from the mouse Encyclopedia of DNA Elements (ENCODE) and explore various applications of the resulting model.
关键词	gene regulation transcription factor regulatory element chromatin regulator chromatin activity
DOI	10.1073/pnas.1704553114
语种	英语
资助项目	Strategic Priority Research Program of the Chinese Academy of Sciences[XDB13000000] ; NIH[R01HG007834] ; NIH[P50HG007735] ; National Natural Science Foundation of China[11422108] ; National Natural Science Foundation of China[61671444] ; National Natural Science Foundation of China[61621003] ; National Natural Science Foundation of China[61573207]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000403687300006
出版者	NATL ACAD SCIENCES
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/25846
专题	应用数学研究所
通讯作者	Jiang, Rui; Wang, Yong; Wong, Wing Hung
作者单位	1.Chinese Acad Sci, Natl Ctr Math & Interdisciplinary Sci, Acad Math & Syst Sci, Beijing 100080, Peoples R China 2.Stanford Univ, Dept Stat, BioX Program, Dept Biomed Data Sci, Stanford, CA 94305 USA 3.Univ Chinese Acad Sci, Sch Math Sci, Beijing 100049, Peoples R China 4.Tsinghua Univ, Minist Educ, Key Lab Bioinformat, Bioinformat Div, Beijing 100084, Peoples R China 5.Tsinghua Univ, Ctr Synthet & Syst Biol, Tsinghua Natl Lab Informat Sci & Technol, Dept Automat, Beijing 100084, Peoples R China
推荐引用方式 GB/T 7714	Duren, Zhana,Chen, Xi,Jiang, Rui,et al. Modeling gene regulation from paired expression and chromatin accessibility data[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2017,114(25):E4914-E4923.
APA	Duren, Zhana,Chen, Xi,Jiang, Rui,Wang, Yong,&Wong, Wing Hung.(2017).Modeling gene regulation from paired expression and chromatin accessibility data.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,114(25),E4914-E4923.
MLA	Duren, Zhana,et al."Modeling gene regulation from paired expression and chromatin accessibility data".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 114.25(2017):E4914-E4923.