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Integrating transcription factor occupancy with transcriptome-wide association analysis identifies susceptibility genes in human cancers

Author

Listed:
  • Jingni He

    (University of Calgary
    Xiangya Hospital, Central South University)

  • Wanqing Wen

    (Vanderbilt University School of Medicine)

  • Alicia Beeghly

    (Vanderbilt University School of Medicine)

  • Zhishan Chen

    (Vanderbilt University School of Medicine)

  • Chen Cao

    (University of Calgary)

  • Xiao-Ou Shu

    (Vanderbilt University School of Medicine)

  • Wei Zheng

    (Vanderbilt University School of Medicine)

  • Quan Long

    (University of Calgary
    University of Calgary
    University of Calgary
    University of Calgary)

  • Xingyi Guo

    (Vanderbilt University School of Medicine
    Vanderbilt University School of Medicine)

Abstract

Transcriptome-wide association studies (TWAS) have successfully discovered many putative disease susceptibility genes. However, TWAS may suffer from inaccuracy of gene expression predictions due to inclusion of non-regulatory variants. By integrating prior knowledge of susceptible transcription factor occupied elements, we develop sTF-TWAS and demonstrate that it outperforms existing TWAS approaches in both simulation and real data analyses. Under the sTF-TWAS framework, we build genetic models to predict alternative splicing and gene expression in normal breast, prostate and lung tissues from the Genotype-Tissue Expression project and apply these models to data from large genome-wide association studies (GWAS) conducted among European-ancestry populations. At Bonferroni-corrected P

Suggested Citation

  • Jingni He & Wanqing Wen & Alicia Beeghly & Zhishan Chen & Chen Cao & Xiao-Ou Shu & Wei Zheng & Quan Long & Xingyi Guo, 2022. "Integrating transcription factor occupancy with transcriptome-wide association analysis identifies susceptibility genes in human cancers," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34888-0
    DOI: 10.1038/s41467-022-34888-0
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