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Enhanced cell deconvolution of peripheral blood using DNA methylation for high-resolution immune profiling

Author

Listed:
  • Lucas A. Salas

    (Geisel School of Medicine, Dartmouth College)

  • Ze Zhang

    (Geisel School of Medicine, Dartmouth College)

  • Devin C. Koestler

    (University of Kansas Medical Center)

  • Rondi A. Butler

    (Brown University)

  • Helen M. Hansen

    (University of California San Francisco)

  • Annette M. Molinaro

    (University of California San Francisco)

  • John K. Wiencke

    (University of California San Francisco
    University of California San Francisco)

  • Karl T. Kelsey

    (Brown University)

  • Brock C. Christensen

    (Geisel School of Medicine, Dartmouth College
    Geisel School of Medicine, Dartmouth College
    Geisel School of Medicine, Dartmouth College)

Abstract

DNA methylation microarrays can be employed to interrogate cell-type composition in complex tissues. Here, we expand reference-based deconvolution of blood DNA methylation to include 12 leukocyte subtypes (neutrophils, eosinophils, basophils, monocytes, naïve and memory B cells, naïve and memory CD4 + and CD8 + T cells, natural killer, and T regulatory cells). Including derived variables, our method provides 56 immune profile variables. The IDOL (IDentifying Optimal Libraries) algorithm was used to identify libraries for deconvolution of DNA methylation data for current and previous platforms. The accuracy of deconvolution estimates obtained using our enhanced libraries was validated using artificial mixtures and whole-blood DNA methylation with known cellular composition from flow cytometry. We applied our libraries to deconvolve cancer, aging, and autoimmune disease datasets. In conclusion, these libraries enable a detailed representation of immune-cell profiles in blood using only DNA and facilitate a standardized, thorough investigation of immune profiles in human health and disease.

Suggested Citation

  • Lucas A. Salas & Ze Zhang & Devin C. Koestler & Rondi A. Butler & Helen M. Hansen & Annette M. Molinaro & John K. Wiencke & Karl T. Kelsey & Brock C. Christensen, 2022. "Enhanced cell deconvolution of peripheral blood using DNA methylation for high-resolution immune profiling," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27864-7
    DOI: 10.1038/s41467-021-27864-7
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    References listed on IDEAS

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    1. Niklas Engels & Lars M. König & Wiebke Schulze & Daniel Radtke & Kanika Vanshylla & Johannes Lutz & Thomas H. Winkler & Lars Nitschke & Jürgen Wienands, 2014. "The immunoglobulin tail tyrosine motif upgrades memory-type BCRs by incorporating a Grb2-Btk signalling module," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
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    Cited by:

    1. Grayson A. Herrgott & James M. Snyder & Ruicong She & Tathiane M. Malta & Thais S. Sabedot & Ian Y. Lee & Jacob Pawloski & Guilherme G. Podolsky-Gondim & Karam P. Asmaro & Jiaqi Zhang & Cara E. Cannel, 2023. "Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Danni A. Gadd & Robert F. Hillary & Daniel L. McCartney & Liu Shi & Aleks Stolicyn & Neil A. Robertson & Rosie M. Walker & Robert I. McGeachan & Archie Campbell & Shen Xueyi & Miruna C. Barbu & Claire, 2022. "Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Jacob Bergstedt & Sadoune Ait Kaci Azzou & Kristin Tsuo & Anthony Jaquaniello & Alejandra Urrutia & Maxime Rotival & David T. S. Lin & Julia L. MacIsaac & Michael S. Kobor & Matthew L. Albert & Darrag, 2022. "The immune factors driving DNA methylation variation in human blood," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    4. J. K. Wiencke & Annette M. Molinaro & Gayathri Warrier & Terri Rice & Jennifer Clarke & Jennie W. Taylor & Margaret Wrensch & Helen Hansen & Lucie McCoy & Emily Tang & Stan J. Tamaki & Courtney M. Tam, 2022. "DNA methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Han Zhang & Rahul Kalla & Jie Chen & Jianhui Zhao & Xuan Zhou & Alex Adams & Alexandra Noble & Nicholas T. Ventham & Judith Wellens & Gwo-Tzer Ho & Malcolm G. Dunlop & Jan Krzysztof Nowak & Yuan Ding , 2024. "Altered DNA methylation within DNMT3A, AHRR, LTA/TNF loci mediates the effect of smoking on inflammatory bowel disease," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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