Immunometabolic changes and potential biomarkers in CFS peripheral immune cells revealed by single-cell RNA sequencing, 2024, Sun et al

Importantly, the highly activated TFs in ME/CFS, such as PSMD8, NFKBIA, PSMD7, NFKB1, REST, TAF7, etc. and MYC, showed significant enrichment in processes related to cell proliferation and differentiation, cellular senescence, infectious diseases, and neurodegenerative diseases like AD and HD, shedding light on potential molecular mechanisms underlying the observed differences.
Noting that the Sweetman Tate paper found a substantial number of their ME/CFS cohort had elevated levels of NFKBIA.

Current Research Provides Insight into the Biological Basis and Diagnostic Potential for ME/CFS. Sweetman et al. (2019)


Aliases for NFKBIA Gene
  • GeneCards Symbol: NFKBIA 2
  • NFKB Inhibitor Alpha 2 3 5
  • IkappaBalpha 2 3 4 5
  • IKBA 2 3 4 5
  • NF-Kappa-B Inhibitor Alpha 2 3 4
  • MAD-3 2 3 5
  • NFKBI 3 4 5
 
Going over this again with a little more understanding (dangerous) and context of other studies and recent discussion.

Is it fair to say there are some questions over some of the conclusions/interpretations here but the general picture of perhaps subtle shifts in the makeup or profile of immune cells and changes in signalling could fit with other ideas and findings? I’m thinking particularly of the skewing in b cell repertoire, idea of immune to neural cell communication, etc
 
The quote is from this thread's paper, Sun et al. Haven't read the full paper yet but in addition to PSMD7 & 8 (non-ATPase regulatory subunits of the 26-S proteasome, not TFs), I think also NFKBIA is an inhibitor of the NF-κB TF complex, not a TF itself. Not familiar with SCENIC but not sure why they're annotated as such - shouldn't they have been caught by the motif filter/analysis?
 
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Thanks @Jonathan Edwards
I find it difficult to distinguish what information may be part of a bigger picture or seen in different light when we have more information and what isn’t. So appreciate the experience of all those with it on the forums in helping do so
 
The quote is from this thread's paper, Sun et al. Haven't read the full paper yet but in addition to PSMD7 & 8 (non-ATPase regulatory subunits of the 26-S proteasome, not TFs), I think also NFKBIA is an inhibitor of the NF-κB TF complex, not a TF itself. Not familiar with SCENIC but not sure why they're annotated as such - shouldn't they have been caught by the motif filter/analysis?
Ah thanks, I forgot SCENIC was used here.

I have used SCENIC myself and ended up abandoning it because of less-than-ideal results. Unless they’ve changed things substantially since I used it, it uses a manually curated long-form list of transcription factors for humans or mice with all the target genes they’re supposed to act on. The list is provided by the package authors if I’m not mistaken.

I’ve only used the mouse version, and I do recall some of the top hits being similarly confusing. It listed Ciita as a transcription factor when that’s just an MHC subunit [edit: activator. Which I suppose you could call a TF if you’re being very loose with the definition, but the target genes were also incorrect]

[edit: and I believe you’re right about NFKBIA]
 
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