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Integrative differential expression and gene set enrichment analysis using summary statistics for scRNA-seq studies

Author

Listed:
  • Ying Ma

    (University of Michigan)

  • Shiquan Sun

    (University of Michigan)

  • Xuequn Shang

    (Northwestern Polytechnical University)

  • Evan T. Keller

    (University of Michigan)

  • Mengjie Chen

    (University of Chicago
    University of Chicago)

  • Xiang Zhou

    (University of Michigan
    University of Michigan)

Abstract

Differential expression (DE) analysis and gene set enrichment (GSE) analysis are commonly applied in single cell RNA sequencing (scRNA-seq) studies. Here, we develop an integrative and scalable computational method, iDEA, to perform joint DE and GSE analysis through a hierarchical Bayesian framework. By integrating DE and GSE analyses, iDEA can improve the power and consistency of DE analysis and the accuracy of GSE analysis. Importantly, iDEA uses only DE summary statistics as input, enabling effective data modeling through complementing and pairing with various existing DE methods. We illustrate the benefits of iDEA with extensive simulations. We also apply iDEA to analyze three scRNA-seq data sets, where iDEA achieves up to five-fold power gain over existing GSE methods and up to 64% power gain over existing DE methods. The power gain brought by iDEA allows us to identify many pathways that would not be identified by existing approaches in these data.

Suggested Citation

  • Ying Ma & Shiquan Sun & Xuequn Shang & Evan T. Keller & Mengjie Chen & Xiang Zhou, 2020. "Integrative differential expression and gene set enrichment analysis using summary statistics for scRNA-seq studies," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15298-6
    DOI: 10.1038/s41467-020-15298-6
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    Cited by:

    1. Jing Nie & Yoshitomo Ueda & Alexander J. Solivais & Eri Hashino, 2022. "CHD7 regulates otic lineage specification and hair cell differentiation in human inner ear organoids," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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