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Cell-type-specific resolution epigenetics without the need for cell sorting or single-cell biology

Author

Listed:
  • Elior Rahmani

    (University of California, Los Angeles)

  • Regev Schweiger

    (Tel Aviv University
    MyHeritage Ltd.)

  • Brooke Rhead

    (University of California, Berkeley)

  • Lindsey A. Criswell

    (University of California, San Francisco)

  • Lisa F. Barcellos

    (University of California, Berkeley)

  • Eleazar Eskin

    (University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles)

  • Saharon Rosset

    (Tel Aviv University)

  • Sriram Sankararaman

    (University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles)

  • Eran Halperin

    (University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles)

Abstract

High costs and technical limitations of cell sorting and single-cell techniques currently restrict the collection of large-scale, cell-type-specific DNA methylation data. This, in turn, impedes our ability to tackle key biological questions that pertain to variation within a population, such as identification of disease-associated genes at a cell-type-specific resolution. Here, we show mathematically and empirically that cell-type-specific methylation levels of an individual can be learned from its tissue-level bulk data, conceptually emulating the case where the individual has been profiled with a single-cell resolution and then signals were aggregated in each cell population separately. Provided with this unprecedented way to perform powerful large-scale epigenetic studies with cell-type-specific resolution, we revisit previous studies with tissue-level bulk methylation and reveal novel associations with leukocyte composition in blood and with rheumatoid arthritis. For the latter, we further show consistency with validation data collected from sorted leukocyte sub-types.

Suggested Citation

  • Elior Rahmani & Regev Schweiger & Brooke Rhead & Lindsey A. Criswell & Lisa F. Barcellos & Eleazar Eskin & Saharon Rosset & Sriram Sankararaman & Eran Halperin, 2019. "Cell-type-specific resolution epigenetics without the need for cell sorting or single-cell biology," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11052-9
    DOI: 10.1038/s41467-019-11052-9
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