Preprint Human Immune Cell Epigenomic Signatures in Response to Infectious Diseases and Chemical Exposures, 2023, Wang et al.

Discussion in 'Other health news and research' started by SNT Gatchaman, Jul 1, 2023.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Human Immune Cell Epigenomic Signatures in Response to Infectious Diseases and Chemical Exposures
    Wenliang Wang; Manoj Hariharan; Anna Bartlett; Cesar Barragan; Rosa Castanon; Vince Rothenberg; Haili Song; Joseph Nery; Andrew Aldridge; Jordan Altshul; Mia Kenworthy; Wubin Ding; Hanqing Liu; Wei Tian; Jingtian Zhou; Huaming Chen; Bei Wei; Irem B Gunduz; Todd Norell; Timothy J Broderick; Micah McClain; Lisa Satterwhite; Thomas Burke; Elizabeth Petzold; Xiling Shen; Chris Woods; Vance G Fowler; Felicia Ruffin; Parinya Panuwet; Dana B Barr; Jennifer L Beare; Anthony K Smith; Rachel R Spurbeck; Sindhu Vangeti; Irene Ramos; German Nudelman; Stuart C Sealfon; Flora Castellino; Anna Maria Walley; Tom Evans; Fabian Muller; William J Greenleaf; Joseph R Ecker

    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.

    Link | PDF (Preprint: BioRxiv)
     
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  2. Hutan

    Hutan Moderator Staff Member

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    If that's true now, or can be in the future, that will be a major advance in environmental medicine. It would be amazing to be able to correlate exposure with illness (along with the underlying inherited genetics).
     
  3. Hutan

    Hutan Moderator Staff Member

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    Nine immune cell types
    Samples of immune cells from 112 donors
    Donors covered specific known viral, bacterial and chemical exposures
    Methylomes, methylomics of the DNA in the nucleus of each cell
    Cell types also differed by exposure group (although the exposure groups probably differed from each other in many ways e.g by age/sex, not just by specific exposure)
    Figure 1 explains the study in pictures. Below is Fig Cii and Ciii.
    Cii - Clustering of cells by methylene, coloured by cell surface markers
    Ciii - Clustering of cells by methlyome, coloured by exposure type
    Screen Shot 2023-07-01 at 5.18.09 pm.png
    It is interesting to see areas of specific colours in Ciii. For pretty much all of the specific exposure groups, it is possible to identify some clustering of specific cell types with specific methylomic profiles.
     
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  4. Hutan

    Hutan Moderator Staff Member

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    The issue exposed and unexposed groups potentially being different in much more than just exposure is not a problem in this analysis, where they used pre-exposure/post-exposure PBMC samples:
    We could do this with pre and post Covid-19 infection samples, for Long Covid and non-Long Covid people. We could do this with ME/CFS samples, tracking changes pre and post exercise. I think we may have seen some limited methylation studies in ME/CFS - we could definitely do with some more.

    Super interesting, thanks for posting it @SNT Gatchaman.
     
  5. Trish

    Trish Moderator Staff Member

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    I haven't read the whole paper, just the bits quoted here. Does it explain how recent the exposure has to be and how long it lasts? Any individual in their lifetime will be exposed to hundreds of infectious agents and chemicals, so how do they single out the effect of one specific agent?
     
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  6. Hutan

    Hutan Moderator Staff Member

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    Change in the methylation of circadian-related genes with HIV infection
    The authors talk about two different methods of determining methylation - I haven't understood the methods. But they report that the methods can find some different things 'highlighting the necessity of using both technologies to profile the epigenomic remodeling'.

    Re HIV, they have samples before and after becoming infected as well as later during treatment, and of course that's a chronic infection. The participants were part of a study that enrolled high risk uninfected individuals and tested them regularly. Around 250 days before infection and 200 days after infection.

    For the flu cohort, they were part of a vaccination study that involved infecting participants with the flu. the post sample was 20 days after infection.

    For the Covid-19 cohort, these participants were all hospitalised, with samples taken during their hospitalisation. I'm not sure when the samples were taken, sounds like within maybe a couple of weeks of infection?

    For the MRSA/MSSA cohort, testing was done when the infection was identified and then 2 or three times after.

    The anthrax sample might indeed have been a bit of a mixed bag. They had been immunised against anthrax but
    :confused: I suspect that if I knew more of what goes on in the world around biological warfare agents, I would sleep quite a lot worse.

    For the organophosphate, they had participants with known levels in urine.
     
  7. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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