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Hard to say. Unfortunately solveME is restructuring their grant program and told me they won’t be accepting applications, possibly it’ll reopen later this year. I’m also looking into pilot grants from my institution, which might be enough to cover a small cohort. It might take a few tries to get...

I may have a bit of a sneaky hunch to that end. As soon as I get my hands on some funding and some ME/CFS samples I can see if my hunch has any substance.

Ah I see from your earlier post that you're probably referring to NME1/2/3. In my searches they came up specifically as transcription factors, particularly for MYC. The interesting thing about all the DNA related hits is that loss of function mutations in them are very strongly associated with...

Unfortunately I'd say the opposite. You're right that there is tons of data, probably even good data that points in the right direction. But the thing about biology is that it is so incredibly context specific. You may find that high levels of protein A suppress protein B in 90% of tissues, but...

Are you talking about the epigenetic regulators (HDAC, DMNT) or other genes? I've been going down the rabbit hole on the epigenetic side

Perhaps this is a better question for another thread, but isn't CD38 expressed on NK cells and also induced in macrophages/monocytes? What reason is there to believe that any response to daratumumab, if it is a real effect, is mediated by B cell depletion rather than simply NK cell depletion? In...

Just to add to what @Jonathan Edwards already explained, we expect a certain amount of linkage disequilibrium simply due to distance on the chromosome. That “shuffling” happens by the two arms of the sister chromatids crossing and then swapping places, so two genes that are next to eachother...

HLA-B and C are usually in strong linkage disequilibrium as well

It’s come up a few times in the virology lab I’m rotating in, it’s particularly important for NK activation and increased expression has been associated with better HIV protection. I don’t think that much is known about mechanism on that front, though. [Edit: for interpretation, I think it’s...

I don’t think so, it survived cross validation plus recapitulation on an independent cohort. It’s likely not a complete story, but I don’t think there’s any reason to disregard it. The math is a little fancy but as a machine learning approach, it’s nothing that I would expect to hallucinate...

Oh that’s weird, nothing was showing up when I clicked on the button before. It must have been resolved when I closed and reopened Firefox. Thanks! These are the corresponding figures for my previous comment:

Thanks again @forestglip for prompting them to provide access.

These points also strike me as interesting, though I would be at a loss to explain what they might all mean functionally. To my amateur eye, it does suggest that any impairment in oxidative phosphorylation is not solely due to SDH inhibition, if it is playing a role. I assume that's why they...

Continuing from the itaconate discussion, I think this is an interesting point. Tomas mentioned that itaconate is only a weak SDH inhibitor, so two options are either that even itaconate's weak effect is sufficient to create the difference shown in this study, or something other than itaconate...

They are quite complex, however they're highly biased by known interactions in the literature. If nobody thought it was interesting to check if protein A binds to protein B, it’s not going to end up in the database even if it’s very relevant to the disease. And the algorithm has a cut off for...

Not necessarily, I think the point of a rare variant analysis is to reaffirm that loss of function in those pathways is in fact critical for disease pathology. It would be a similar logic as doing a knockout study in a mouse. If you have experimental results that suggest a gene is involved in...

It was nearly the same as their AUC on their training cohort, which is impressive in itself. I would lose confidence if it was a high AUC in training and near 0.5 in test. While weaker, the training AUC is about what I’d expect from a rare variant analysis on a smaller cohort.

An important point is that the HEAL2 algorithm leverages the STING database to incorporate protein-protein interactions in its attention mechanism. What this means for interpretation is that multiple genes that are all part of the same network are likely to score higher cumulatively. Therefore...

That sort of thing seems to come up a lot in chronic illnesses—a mutation that would be deleterious if homozygous, and should be fine if heterozygous, but obviously isn’t under some perfect storm of homeostatic stress. It’s always the assumption that the non-deleterious allele should be able to...

Also I take back my critique about cytotoxic CD4s—I just noticed that the dot plot in figure 4 shows CD4. I must not have been able to read the tiny text when I was looking at the figures on my phone. generally I still prefer to show markers as feature plots since only a proportion of cells in...