Human Immune Cell Epigenomic Signatures in Response to Infectious Diseases and Chemical Exposures

• Type of Material: Article
• Authors: Wenliang Wang, Salk Institute for Biological Studies; Manoj Hariharan, Salk Institute for Biological Studies; Anna Bartlett, Salk Institute for Biological Studies; Cesar Barragan, Salk Institute for Biological Studies; Rosa Castanon, Salk Institute for Biological Studies; Vince Rothenberg, Salk Institute for Biological Studies; Haili Song, Salk Institute for Biological Studies; Joseph Nery, Salk Institute for Biological Studies; Andrew Aldridge, Duke University; Jordan Altshul, Salk Institute for Biological Studies; Mia Kenworthy, Salk Institute for Biological Studies; Wubin Ding, Salk Institute for Biological Studies; Hanqing Liu, Salk Institute for Biological Studies; Wei Tian, Salk Institute for Biological Studies; Jingtian Zhou, Salk Institute for Biological Studies; Huaming Chen, Salk Institute for Biological Studies; Bei Wei, Stanford University; Irem B Gunduz, Saarland University; Todd Norell, Florida Institute for Human and Machine Cognition; Timothy J Broderick, Florida Institute for Human and Machine Cognition; Micah T McClain, Duke University; Lisa L Satterwhite, Duke University; Thomas W Burke, Duke University; Elizabeth A Petzold, Duke University; Xiling Shen, Terasaki Institute for Biomedical Innovation; Christopher W Woods, Duke University; Vance G Fowler Jr, Duke University; Felicia Ruffin, Duke University; Parinya Panuwet, Emory University; Dana B Barr, Emory University; Jennifer L Beare, Battelle Memorial Institute; Anthony K Smith, Battelle Memorial Institute; Rachel R Spurbeck, Battelle Memorial Institute; Sindhu Vangeti, Icahn School of Medicine at Mount Sinai; Irene Ramos, Icahn School of Medicine at Mount Sinai; German Nudelman, Icahn School of Medicine at Mount Sinai; Stuart C Sealfon, Icahn School of Medicine at Mount Sinai; Flora Castellino, Biomedical Advanced Research and Development Authority, Washington; Anna Maria Walley, Vaccitech plc, United Kingdom; Thomas Evans, Vaccitech plc, United Kingdom; Fabian Muller, Saarland University; William J Greenleaf, Stanford University; Joseph R Ecker, Salk Institute for Biological Studies
• Language: English
• Date: 2023-06-30
• Publisher: NIH
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1101/2023.06.29.546792
• Title of Journal or Parent Work: bioRxiv
• Keywords: Epigenome; DNA methylation; Infection; Exposure; Immune cells
• Research Categories: Health Sciences, Pathology; Environmental Sciences; Health Sciences, Immunology; Health Sciences, Toxicology

Abstract

Variations in DNA methylation patterns in human tissues have been linked to various environmental exposures and infections. Here, we identified the DNA methylation signatures associated with multiple exposures in nine major immune cell types derived from peripheral blood mononuclear cells (PBMCs) at single-cell resolution. We performed methylome sequencing on 111,180 immune cells obtained from 112 individuals who were exposed to different viruses, bacteria, or chemicals. Our analysis revealed 790,662 differentially methylated regions (DMRs) associated with these exposures, which are mostly individual CpG sites. Additionally, we integrated methylation and ATAC-seq data from same samples and found strong correlations between the two modalities. However, the epigenomic remodeling in these two modalities are complementary. Finally, we identified the minimum set of DMRs that can predict exposures. Overall, our study provides the first comprehensive dataset of single immune cell methylation profiles, along with unique methylation biomarkers for various biological and chemical exposures.