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

OK makes sense. If you have any set of genes that appear to be important please tag me so I can have a look at them.

 

Understandable. I’m sure we all have this concern to varying degrees. There are various things they could and probably will try.

But it’s good we have the environment here and some good scientists with which we can explore it. And ultimately I think we’re best served by getting on with good science and that will ultimately beat the bad in both quality and quantity.

 

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 though, so I'm searching for more evidence to back it up

 

in the LCLs, proteasome subunits were predominantly upregulated (https://www.mdpi.com/1422-0067/22/4/2046 figure 8, damn but my old figures were ugly). We have gene expression data from other cell types too now, but this aspect hasn't been specifically analysed yet so I can't comment on it

are you thinking along the lines of autophagy or more specific to the proteasome?

 

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 thinking ubiquitin ligases might be at fault. But the other possibility is that failure to degrade certain proteins at a critical point is simply a byproduct of having too many proteins to degrade overall, in which case I would expect increased proteasome subunit expression as an attempt to compensate. Did you happen to see any other evidence of UPR?

 

Haven't noticed it standing out but haven't looked at the GSEA in the other datasets in detail yet, nor at UPR in the old data in more detail than published

 

Are you thinking generally @jnmaciuch or that this is an issue in specific places? Say, issues around degradation of neurotransmitters or other proteins by the proteasome around the synapse?

 

@jnmaciuch check out the following thread reply on X/Twitter which may be of interest regarding ubiquitin ligase :

https://twitter.com/user/status/1895026389646221621

 

Just a suggestion, but many of us simply don't use Twitter anymore, and find it annoying as Twitter greatly limits what you can read without logging in - it doesn't let us read the replies for example.

I know you have an account on Bsky but haven't used the account since 2023. Just a suggestion anyway.

 

I’d echo that. Or post threads using threadreader or something without any barriers? I haven’t been on twitter for many years and won’t be signing up just to read things as you seem to need to do these days.

 

Yes unfortunately I don’t have an account and can’t read this

 

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.

thanks to @DMissa for the extra info!

 

Understood @jnmaciuch I look forward to hearing if/when you have something more to share