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  1. jnmaciuch

    Comparing DNA Methylation Landscapes in Peripheral Blood from [ME/CFS] and Long COVID Patients, 2025, Peppercorn et al

    A little over and under 10%, respectively. So there’s a lot of noise even when selecting down to 70K, probably to be expected
  2. jnmaciuch

    Comparing DNA Methylation Landscapes in Peripheral Blood from [ME/CFS] and Long COVID Patients, 2025, Peppercorn et al

    I’m also realizing just now that I have a tendency to use food metaphors when discussing science close to dinner time. I’m a caricature of myself
  3. jnmaciuch

    Comparing DNA Methylation Landscapes in Peripheral Blood from [ME/CFS] and Long COVID Patients, 2025, Peppercorn et al

    For what it’s worth, the full PCA does actually tell an interesting story along PC2—the fact that there are distinct “Neapolitan stripes” between the three groups, despite some messy outliers, is impressive since it is actually taking into consideration all 70K sites (even despite the fact that...
  4. jnmaciuch

    Comparing DNA Methylation Landscapes in Peripheral Blood from [ME/CFS] and Long COVID Patients, 2025, Peppercorn et al

    The methods mention that they used the WHO's 2021 case definition, which says this: So the described features are ME/CFS-like, certainly, if you do not take into account degree of severity or post exertional malaise (considered to be the hallmark characteristic of ME/CFS, if you are...
  5. jnmaciuch

    Comparing DNA Methylation Landscapes in Peripheral Blood from [ME/CFS] and Long COVID Patients, 2025, Peppercorn et al

    I have been able to view the PCA on the 70K sites. I don't have permission to share the image itself, but I do have permission to describe it. As expected, much much less clean separation between groups, all the points are quite dispersed through the 2D space. PC2 gives hints of separation by...
  6. jnmaciuch

    Preprint Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis, 2025, Zhang+

    I think it’s more than likely that brain tissue is involved in someway but the issue I’m toying with would not be exclusive to the brain or nerves. Again, sorry to be so vague, even for my idle speculations I prefer to have a couple pieces of evidence to back it up before I put it out there...
  7. jnmaciuch

    Comparing DNA Methylation Landscapes in Peripheral Blood from [ME/CFS] and Long COVID Patients, 2025, Peppercorn et al

    I just got a response from the corresponding author, he confirmed that figure 2 is only on significant sites. I've asked if he would mind sharing the PCA on all sites with me. He said that it was more blurry (as you'd expect) but there was still separation between groups.
  8. jnmaciuch

    Preprint Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis, 2025, Zhang+

    Thanks! That's really interesting. More specific to the proteasome, or rather, failure to (adequately) degrade particular proteins post viral infection. I still have several details that need to be ironed out, so apologies for being vague. It may not be the proteasome itself--I was initially...
  9. jnmaciuch

    Comparing DNA Methylation Landscapes in Peripheral Blood from [ME/CFS] and Long COVID Patients, 2025, Peppercorn et al

    I briefly saw something about this when I was trying to find the corresponding author's email--from the first news article that came up, it looks like his family member has ME/CFS and he also has trainees with mild ME in his lab.
  10. jnmaciuch

    Itaconate modulates immune responses via inhibition of peroxiredoxin 5, 2025, Tomas Paulenda et al

    It is, but from my prior work in macrophages I have never seen it being stimulated by IFNAR or IFNGR activation alone. In macrophages, this is induced via co-stimulation of interferons and LPS, or another TLR activator [edit: leading to both Nf-kB and STAT TF binding to facilitate ACOD1...
  11. jnmaciuch

    Itaconate modulates immune responses via inhibition of peroxiredoxin 5, 2025, Tomas Paulenda et al

    Thank you, I am quite aware of all of this, local interferon signaling is my research focus at the moment and exactly what I was referencing in my previous post. My point re: itaconate and SDH was towards local metabolic dysregulation in neighboring cells in response to viral infection [edit...
  12. jnmaciuch

    Itaconate modulates immune responses via inhibition of peroxiredoxin 5, 2025, Tomas Paulenda et al

    Thank you, yes I fully understand that, my point was mainly to address the issue of “infected cells and neighboring cells” per your previous post. All the evidence I’ve seen of viral infection leading to altered metabolic environment in nearby cells is mediated through locally activated immune...
  13. jnmaciuch

    Preprint Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis, 2025, Zhang+

    Are you at liberty to give more details on exactly what you're finding? I was initially inclined to believe that proteasome findings would be the result of general homeostatic stress like you mentioned, but recently I have more reason to believe they might be directly involved. It's just a hunch...
  14. jnmaciuch

    ME/CFS as a biological information processing problem

    Thanks for the further info. I am happy to say that the signal is more likely some oligomer attached to nerves, though like @chillier, I just don't see what the story would be with that signal increasing at 24 hours post-exercise. Hence why I was interested in mtDNA, as that would be much more...
  15. jnmaciuch

    Itaconate modulates immune responses via inhibition of peroxiredoxin 5, 2025, Tomas Paulenda et al

    This certainly fits with other threads that I have been running down in my own research. However, the main concern would be whether non-myeloid cells actually upregulate IRG1 to a sufficient extent to cause the level of TCA cycle dysregulation you hypothesize. Tomas noted that other findings...
  16. jnmaciuch

    Comparing DNA Methylation Landscapes in Peripheral Blood from [ME/CFS] and Long COVID Patients, 2025, Peppercorn et al

    Yes that piqued my interest for the same reason, though I’m definitely trying not to get too excited when this is a very preliminary study.
  17. jnmaciuch

    Comparing DNA Methylation Landscapes in Peripheral Blood from [ME/CFS] and Long COVID Patients, 2025, Peppercorn et al

    I haven’t done a DNA methylation analysis like this paper but I do have comparable experience from ATAC-seq which looks at open chromatin (another epigenetic modification that uses similar protocols for sequencing). That study used 3 replicates on old vs. young mice. Even using genetically...
  18. jnmaciuch

    Comparing DNA Methylation Landscapes in Peripheral Blood from [ME/CFS] and Long COVID Patients, 2025, Peppercorn et al

    I think there is a discrepancy between what the text says and what the figure legend says. I initially had the same concern as you that they might be pre-selecting the features that would make the findings look best, so I checked the text and saw this: This certainly suggested to me that all...
  19. jnmaciuch

    Preprint Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis, 2025, Zhang+

    It just refers to all the signaling that happens as a result of the NOTCH protein binding to one of its ligands, which is a pretty broad category. It’s involved in a lot of biological processes, most notably in early embryonic development and growth, which is why mutations in it are highly...
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