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Time course regulatory analysis based on paired expression and chromatin accessibility data
Duren, Zhana1; Chen, Xi1; Xin, Jingxue1; Wang, Yong2,3; Wong, Wing Hung1,4
2020-04-01
Source PublicationGENOME RESEARCH
ISSN1088-9051
Volume30Issue:4Pages:622-634
AbstractA 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.
DOI10.1101/gr.257063.119
Indexed BySCI
Language英语
Funding ProjectNational 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 Research AreaBiochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity
WOS SubjectBiochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity
WOS IDWOS:000530027100010
PublisherCOLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
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Document Type期刊论文
Identifierhttp://ir.amss.ac.cn/handle/2S8OKBNM/51403
Collection应用数学研究所
Corresponding AuthorWang, Yong; Wong, Wing Hung
Affiliation1.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
Recommended Citation
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.
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