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Inferring transcriptional regulators through integrative modeling of public chromatin accessibility and ChIP-seq data

Qian Qin, Jingyu Fan, Rongbin Zheng, Changxin Wan, Shenglin Mei, Qiu Wu, Hanfei Sun, Jing Zhang, Myles Brown, Clifford A. Meyer, X. Shirley Liu
doi: https://doi.org/10.1101/846139
Qian Qin
1Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
2Children’s hospital of Fudan University, Center of Molecular Medicine, Shanghai 201102, China
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Jingyu Fan
1Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Rongbin Zheng
1Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Changxin Wan
1Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Shenglin Mei
1Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Qiu Wu
1Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Hanfei Sun
1Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Jing Zhang
3School of Life Science and Technology, Tongji University, Shanghai 200065, China
4Stem Cell Translational Research Center, Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai 200065, China
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  • For correspondence: cliff_meyer@ds.dfci.harvard.edu xsliu@ds.dfci.harvard.edu zhangjing@tongji.edu.cn
Myles Brown
5Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA
6Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA
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Clifford A. Meyer
5Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA
7Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02215, USA
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  • For correspondence: cliff_meyer@ds.dfci.harvard.edu xsliu@ds.dfci.harvard.edu zhangjing@tongji.edu.cn
X. Shirley Liu
1Shanghai Key Laboratory of Tuberculosis, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
5Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA
7Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02215, USA
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  • For correspondence: cliff_meyer@ds.dfci.harvard.edu xsliu@ds.dfci.harvard.edu zhangjing@tongji.edu.cn
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Abstract

We developed Lisa (http://lisa.cistrome.org) to predict the transcriptional regulators (TRs) of differentially expressed or co-expressed gene sets. Based on the input gene sets, Lisa first uses compendia of public histone mark ChIP-seq and chromatin accessibility profiles to construct a chromatin model related to the regulation of these genes. Then using TR ChIP-seq peaks or imputed TR binding sites, Lisa probes the chromatin models using in silico deletion to find the most relevant TRs. Applied to gene sets derived from targeted TF perturbation experiments, Lisa boosted the performance of imputed TR cistromes, and outperformed alternative methods in identifying the perturbed TRs.

Footnotes

  • http://lisa.cistrome.org/

  • List of abbreviations

    TF
    transcription factor
    CR
    chromatin regulator
    TR
    transcriptional regulator
    RP
    regulatory potential
    ISD
    in silico deletion
    ROC
    receiver operator characteristic
    AUC
    area under curve
    ChIP-seq
    chromatin immunoprecipitation followed by DNA sequencing
    DNase-seq
    DNase I digestion followed by DNA sequencing
    H3K27ac
    histone H3 lysine 27 acetylation
    AR
    Androgen Receptor
    ER
    Estrogen Receptor
    GR
    Glucocorticoid Receptor
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    Posted November 18, 2019.
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    Inferring transcriptional regulators through integrative modeling of public chromatin accessibility and ChIP-seq data
    Qian Qin, Jingyu Fan, Rongbin Zheng, Changxin Wan, Shenglin Mei, Qiu Wu, Hanfei Sun, Jing Zhang, Myles Brown, Clifford A. Meyer, X. Shirley Liu
    bioRxiv 846139; doi: https://doi.org/10.1101/846139
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    Inferring transcriptional regulators through integrative modeling of public chromatin accessibility and ChIP-seq data
    Qian Qin, Jingyu Fan, Rongbin Zheng, Changxin Wan, Shenglin Mei, Qiu Wu, Hanfei Sun, Jing Zhang, Myles Brown, Clifford A. Meyer, X. Shirley Liu
    bioRxiv 846139; doi: https://doi.org/10.1101/846139

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