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-Log10(p-value) is the standard choice for plotting things like enrichment of a bunch of pathways or a volcano plot, since FDR correction will leave you with a lot of redundant values. It's recommended to just use an additional visual indicator for which ones passed FDR or mention in the...

I'm sure a lot of work went into this paper. I also could not remotely follow what was being talked about between one figure at the next (and I'm pretty used to lengthy -omics analyses).

Ah my bad! I thought that was the paragraph talking about Fig 2 not Fig 1 (since the bar plot showed some pathways having 1 lipid hit). I agree that having one upregulated metabolite doesn’t mean there’s evidence for enrichment of the whole pathway—I appreciate the text was upfront about there...

I don’t want to speak over Daniel but from the methods it seems like imputation was only used for the specific step of pathway analysis using MetaboAnalyst—individual feature comparisons would not use imputation. It’s possible for imputation to skew enrichment of some pathways if controls had a...

Interesting, that does seem to address some of the unanswered questions in this study.

I’m sorry I don’t quite know what you mean. [Edit: I don’t think any chronic disease model is talking about a “single point of failure” except genetic disorders and that’s not what I’ve been discussing?] Maybe best to leave the conversation where it’s at to avoid derailing the thread.

One option would be that if you already had good reason to think a certain pathway was involved, you could try inducing it in cells and see if you end up with the same phenotype. Or you could do an unbiased screen looking for epigenetic differences and see if any of them have been previously...

It's an additional piece of support, though worth keeping in mind that every DecodeME hit had a very small OR (difference compared to controls). It's not just a matter of precision but more of coherence, where you can sort through a million potential connections to a hypothesis of how that...

The only thing that would be unique for B cells is the specific “wiring”—it is entirely likely that these suites of genes (or specific subsets of them) can be upregulated together in other cell types, but they would be responsive to different triggers. T cells might be the closest to the B cell...

That's what keeps us in business ;) For those who get into science to find answers instead of peddling narratives, anyways

Unfortunately it's a difficult position to piece things together from. What you can do with any transcriptomics data is take a list of differentially expressed genes and cross reference it with databases that list hundreds of transcription factors and their known target genes in different cell...

Theoretically possible that they are involved, though it is hard to make sense of how they are driving the illness. Just considering the limited amount of surface receptors that those papers looked at and trying to occams-razor it, it seems more likely that those findings are another downstream...

Overhauling of lipid metabolism is a necessary step in B cell maturation because B cell receptors require lipid rafts. What that means on a transcriptional level is B cells are specially "wired" such that whole suites of lipid related genes are upregulated in concert with other genes that...

Maybe! I don't really have a way to connect them since there are so few findings on that specific aspect of BTN

It might be relevant. Though I think it might be making too many assumptions to interpret these findings as necessarily a problem with B cell membranes. B cell lipid metabolism is supposed to shift quite dynamically throughout its developmental trajectory. And like I said above, if there truly...

Hi @TamaraRC thanks for your sharing your thoughts! I think this is an interesting way to come at the idea. The main issue I see is that reinforcement-of-metabolic-state in immune cells is something that is highly contextual and specific to the lifespan of various immune cell subsets. B cells at...

That’s interesting! The other known non-lymphocyte-related function of butyrophilins is in facilitating globule production for milk secretion—wouldn’t be relevant in non-mammals obviously, though may have implications for butyrophilins in other roles related to lipid membrane regulation. This...

Merged posts from thread Rational hope of treatment? ----------------- Perhaps a rare variant could be useful information but the method in that paper is unlikely to point us to the useful ones. From the replies it’s clear that it was starting with the hypothesis that there is no one such...

Thanks for your willingness to go back and forth. I see you're in the genetics and bioinformatics department! I'm doing my PhD in bioinformatics, glad to have someone with your background join the forum! Discussions on here tend to trend towards the critical side--I've found it really useful for...

The theory is bystander activation not bystander autoimmunity—just referring to the fact that those autoreactive lymphocytes may get activated by proximity to the local infection response