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

Wenliang WangManoj HariharanAnna BartlettCesar BarraganRosa CastanonVince RothenbergHaili SongJoseph NeryAndrew AldridgeJordan AltshulMia KenworthyWubin DingHanqing LiuWei TianJingtian ZhouHuaming ChenBei WeiIrem B GündüzTodd NorellTimothy J BroderickMicah T McClainLisa L SatterwhiteThomas W BurkeElizabeth A PetzoldXiling ShenChristopher W WoodsVance G FowlerFelicia RuffinParinya PanuwetDana B BarrJennifer L BeareAnthony K SmithRachel R SpurbeckSindhu VangetiIrene RamosGerman NudelmanStuart C SealfonFlora CastellinoAnna Maria WalleyThomas EvansFabian MüllerWilliam J GreenleafJoseph R Ecker
Published in: bioRxiv : the preprint server for biology (2023)
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.
Keyphrases
  • dna methylation
  • genome wide
  • air pollution
  • single cell
  • gene expression
  • endothelial cells
  • infectious diseases
  • copy number
  • big data
  • risk assessment
  • climate change
  • single molecule
  • human health