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

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.

Déclaration de conflit d'intérêts

Declaration of Interests Application for patent based on the results from this work has been filed with USPTO with application number US 63/489,546. J.R.E. is a scientific advisor for Zymo Research Inc. and Ionis Pharmaceuticals. W.J.G. is named as an inventor on patents describing ATAC-seq methods. 10X Genomics has licensed intellectual property on which W.J.G. is listed as an inventor. W.J.G. holds options in 10X Genomics and is a consultant for Ultima Genomics and Guardant Health. W.J.G. is a scientific co-founder of Protillion Biosciences. V.G.F. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche, grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius; Genentech, Regeneron, Deep Blue, Basilea, Janssen; royalties from UpToDate, stock options from Valanbio and ArcBio, honoraria from Infectious Diseases of America for his service as Associate Editor of Clinical Infectious Diseases, and a patent for sepsis diagnostics pending. S.C.S. is scientific founder and serve as Chief Scientific Officer of GNOMX Corp.