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Cellular Heterogeneity–Adjusted cLonal Methylation (CHALM) improves prediction of gene expression

Author

Listed:
  • Jianfeng Xu

    (University of California
    Baylor College of Medicine)

  • Jiejun Shi

    (University of California)

  • Xiaodong Cui

    (Baylor College of Medicine)

  • Ya Cui

    (University of California)

  • Jingyi Jessica Li

    (University of California)

  • Ajay Goel

    (Beckman Research Institute of City of Hope)

  • Xi Chen

    (Baylor College of Medicine)

  • Jean-Pierre Issa

    (The Coriell Institute for Medical Research)

  • Jianzhong Su

    (Baylor College of Medicine)

  • Wei Li

    (University of California)

Abstract

Promoter DNA methylation is a well-established mechanism of transcription repression, though its global correlation with gene expression is weak. This weak correlation can be attributed to the failure of current methylation quantification methods to consider the heterogeneity among sequenced bulk cells. Here, we introduce Cell Heterogeneity–Adjusted cLonal Methylation (CHALM) as a methylation quantification method. CHALM improves understanding of the functional consequences of DNA methylation, including its correlations with gene expression and H3K4me3. When applied to different methylation datasets, the CHALM method enables detection of differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms.

Suggested Citation

  • Jianfeng Xu & Jiejun Shi & Xiaodong Cui & Ya Cui & Jingyi Jessica Li & Ajay Goel & Xi Chen & Jean-Pierre Issa & Jianzhong Su & Wei Li, 2021. "Cellular Heterogeneity–Adjusted cLonal Methylation (CHALM) improves prediction of gene expression," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20492-7
    DOI: 10.1038/s41467-020-20492-7
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    Cited by:

    1. Shirong Zhang & Shutao He & Xin Zhu & Yunfei Wang & Qionghuan Xie & Xianrang Song & Chunwei Xu & Wenxian Wang & Ligang Xing & Chengqing Xia & Qian Wang & Wenfeng Li & Xiaochen Zhang & Jinming Yu & She, 2023. "DNA methylation profiling to determine the primary sites of metastatic cancers using formalin-fixed paraffin-embedded tissues," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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