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The only thing that wouldn’t make sense to me then is the few points scattered inside the cytosol of muscle cells. Granted it’s only a few points, but some are at the same intensity as the signal in the matrix so I don’t feel like I can completely write them off. Given the lack of specificity of...

That's pretty impressive separation on the PCA

If you know R I could probably give you a rough outline on how to do it. [Edit: also, sadly, much of the work that I have to do for school/research is much less productive and useful than the ME/CFS rabbitholes I'd prefer to spend my time on...such is life]

You're exactly right, it seems I was conflating details from different sections. Using the bigger graph to begin with would alleviate some of the "junk module" concern since you ideally wouldn't be left with too many miscellaneous stragglers. Technically you could use those modules as custom...

I am not sure what new information Wust is using to exclude the possibility of nerve fibers in his brief answers to me. Does this completely preclude the possibility of free-floating aggregated mtDNA?

Louvain is basically what you as a human would do if you printed out a graph and then drew circles around nodes to group them together discretely. The algorithm just applies a certain logic for the best way to "cut" the graph. It looks like what they did is pull the graph information from...

I actually couldn't figure that out from the text. My guess is that it might be based on the actual attention score with some kolmogorov-smirnov-like test compared to random permutations, but I definitely don't know the specifics. I think the low amount of mutations for each gene in this dataset...

Oh sorry that's an implicit bit of information that I didn't think to specify--the networks in STRING are not discrete like lists in gene sets. Think of STRING more as one giant nearest neighbor graph, if you're more familiar with that. All the known protein interactions are encoded as edges...

I think the main issue is just that the attentional mechanism leverages the PPI network so that a list ranked by attention will be inherently skewed by inflated attention across networks of interconnected genes. The network structure ends up pulling related genes higher up the attention ranking...

Sorry, I’m having a bit of trouble understanding what you mean here. Which oligomers are you suggesting? To me it seems linear only insofar as it is following the boundaries between cells in the extracellular space (plus many dots in the cytosol itself, which would not be nerves)

Do you have another possible candidate for the ThT binding? Iirc the acetylcholinesterase binding is driven by a particular structure arising from aromatic residues [edit: in the binding pocket]. I’m not aware of another neuronal protein that would bind to ThT in this way, but I may have just...

In my opinion it wouldn’t be completely kosher to use GSEA on this data. The intended use case of GSEA (RNA-seq) has an implicit assumption of independence—while you might expect levels of gene A to influence levels of gene B biologically, your ability to measure the fold change of each gene and...

scATAC-seq on its own is a possibility, the issue would be that the proportion of immune cells in a muscle biopsy sample would already be low, and by doing single cell instead of bulk you’re losing a lot of depth. So your signal of interest would need to be very stark with low variability, which...

There would be a way to indirectly connect mtDNA to synapses via extracellular calcium however, since mtDNA release occurs through VDAC1, which is first and foremost a calcium ion channel and its oligomerization is sensitive to calcium levels controlled by local neurons. I’ll note that many of...

I recently reached out to Rob, and he said they had some further evidence that it was not nerves, but exact confirmation would be forthcoming. The reason I reached out to him was the possibility that the signal was not amyloid or acetylcholinesterase, but actually extra-mitochondrial mtDNA...

I am not too sure about the role of sleep wake cycle specifically, but it has already been shown that there seem to be “phases” of immune response to various stimuli, some of which occur at earlier phases and some of which only peak at ~24-48 hours. some discussion of that is here...

Just to put it out there, we know from interferon therapies that you really do get the whole shebang of fatigue-fever-chills-pain-etc. from a single circulating interferon. What’s happening in actual viral infection is undoubtedly more complex. But the effect of a single interferon does quite...

Looks like we both misremembered! I may have assumed it was Bonferroni because the p values were so negligible.

I remember also being confused why on earth they would use Bonferroni for an -omics analysis. You almost always want to use Benjamini-hochberg (FDR correction), because if you’re doing Bonferroni for so many analytes you’re basically throwing the baby out with the bath water. Like @forestglip...

This has been my experience trying (and failing) to use it for research. It’s good for tasks where the sheer amount of data to sort through is unreasonable for one person and you aren’t relying on the accuracy of the results. Which only happens to cover vanishingly few tasks in my work. It...