Time course regulatory analysis based on paired expression and chromatin accessibility data

doi:10.1101/gr.257063.119

CORC > 数学与系统科学研究院 > 中国科学院数学与系统科学研究院 > 应用数学研究所

	Time course regulatory analysis based on paired expression and chromatin accessibility data
	Duren, Zhana 2; Chen, Xi 2; Xin, Jingxue 2; Wang, Yong 1,3; Wong, Wing Hung 2,4
刊名	GENOME RESEARCH
	2020-04-01
卷号	30 期号:4 页码:622-634
ISSN号	1088-9051
DOI	10.1101/gr.257063.119
英文摘要	A time course experiment is a widely used design in the study of cellular processes such as differentiation or response to stimuli. In this paper, we propose time course regulatory analysis (TimeReg) as a method for the analysis of gene regulatory networks based on paired gene expression and chromatin accessibility data from a time course. TimeReg can be used to prioritize regulatory elements, to extract core regulatory modules at each time point, to identify key regulators driving changes of the cellular state, and to causally connect the modules across different time points. We applied the method to analyze paired chromatin accessibility and gene expression data from a retinoic acid (RA)-induced mouse embryonic stem cells (mESCs) differentiation experiment. The analysis identified 57,048 novel regulatory elements regulating cerebellar development, synapse assembly, and hindbrain morphogenesis, which substantially extended our knowledge of cis-regulatory elements during differentiation. Using single-cell RNA-seq data, we showed that the core regulatory modules can reflect the properties of different subpopulations of cells. Finally, the driver regulators are shown to be important in clarifying the relations between modules across adjacent time points. As a second example, our method on Ascl1-induced direct reprogramming from fibroblast to neuron time course data identified Id1/2 as driver regulators of early stage of reprogramming.
资助项目	National Institutes of Health (NIH)[R01HG010359] ; National Institutes of Health (NIH)[P50HG007735] ; National Natural Science Foundation of China (NSFC)[11871463] ; National Natural Science Foundation of China (NSFC)[61671444] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB13000000]
WOS研究方向	Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity
语种	英语
出版者	COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
WOS记录号	WOS:000530027100010
内容类型	期刊论文
源URL	[http://ir.amss.ac.cn/handle/2S8OKBNM/51402]
专题	应用数学研究所
通讯作者	Wang, Yong; Wong, Wing Hung
作者单位	1.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China 2.Stanford Univ, Dept Stat, Stanford, CA 94305 USA 3.Chinese Acad Sci, Acad Math & Syst Sci, MDIS, CEMS,NCMIS, Beijing 100080, Peoples R China 4.Stanford Univ, Ctr Personal Dynam Regulomes, Dept Biomed Data Sci, Bio X Program, Stanford, CA 94305 USA
推荐引用方式 GB/T 7714	Duren, Zhana,Chen, Xi,Xin, Jingxue,et al. Time course regulatory analysis based on paired expression and chromatin accessibility data[J]. GENOME RESEARCH,2020,30(4):622-634.
APA	Duren, Zhana,Chen, Xi,Xin, Jingxue,Wang, Yong,&Wong, Wing Hung.(2020).Time course regulatory analysis based on paired expression and chromatin accessibility data.GENOME RESEARCH,30(4),622-634.
MLA	Duren, Zhana,et al."Time course regulatory analysis based on paired expression and chromatin accessibility data".GENOME RESEARCH 30.4(2020):622-634.