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

文献类型：期刊论文

作者Duren, Zhana1; Chen, Xi1; Xin, Jingxue1; Wang, Yong2,3; Wong, Wing Hung1,4
刊名GENOME RESEARCH
出版日期2020-04-01
卷号30期号:4页码:622-634
ISSN号1088-9051
DOI10.1101/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
WOS记录号WOS:000530027100010
出版者COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
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.Stanford Univ, Dept Stat, Stanford, CA 94305 USA
2.Chinese Acad Sci, Acad Math & Syst Sci, MDIS, CEMS,NCMIS, Beijing 100080, Peoples R China
3.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, 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.

入库方式： OAI收割

来源：数学与系统科学研究院

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