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An analytical framework for decoding cell type-specific genetic variation of gene regulation

Author

Listed:
  • Yanyu Xiao

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center)

  • Jingjing Wang

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center)

  • Jiaqi Li

    (Zhejiang University School of Medicine)

  • Peijing Zhang

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center)

  • Jingyu Li

    (Zhejiang University School of Medicine)

  • Yincong Zhou

    (Zhejiang University)

  • Qing Zhou

    (Zhejiang University)

  • Ming Chen

    (Zhejiang University)

  • Xin Sheng

    (Zhejiang University Medical Center)

  • Zhihong Liu

    (Zhejiang University Medical Center)

  • Xiaoping Han

    (Zhejiang University School of Medicine
    Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine)

  • Guoji Guo

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine
    Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University)

Abstract

A deeper understanding of genetic regulation and functional mechanisms underlying genetic associations with complex traits and diseases is impeded by cellular heterogeneity and linkage disequilibrium. To address these limits, we introduce Huatuo, a framework to decode genetic variation of gene regulation at cell type and single-nucleotide resolutions by integrating deep-learning-based variant predictions with population-based association analyses. We apply Huatuo to generate a comprehensive cell type-specific genetic variation landscape across human tissues and further evaluate their potential roles in complex diseases and traits. Finally, we show that Huatuo’s inferences permit prioritizations of driver cell types associated with complex traits and diseases and allow for systematic insights into the mechanisms of phenotype-causal genetic variation.

Suggested Citation

  • Yanyu Xiao & Jingjing Wang & Jiaqi Li & Peijing Zhang & Jingyu Li & Yincong Zhou & Qing Zhou & Ming Chen & Xin Sheng & Zhihong Liu & Xiaoping Han & Guoji Guo, 2023. "An analytical framework for decoding cell type-specific genetic variation of gene regulation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39538-7
    DOI: 10.1038/s41467-023-39538-7
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    References listed on IDEAS

    as
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