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No, sorry for not being clear, I was talking about the symptoms attributed to the variants in your table I think the core of the disagreement is the level of uncertainty that the identified variants from an n-of-1 analysis actually explain any of the symptoms identified when the participant...

Missing values are common in mass spec, usually an error of peak detection, deconvolution, etc. Number of missing values was not stated but Daniel (the author) confirmed on this thread that there was no missingness for several of the highlighted features

I suppose this point will have to wait for confirmation of what exactly the evidence is that the heterozygous mutations do present with those laundry lists of symptoms, since mostly what I was finding was that the homozygous state might look something like ME/CFS but the heterozygous state...

I think your table might have a problem with every reference number being for the wrong paper. I wanted to go through and read your references to see what I was missing since the majority of my searching found that heterozygous individuals for those identified genes did not have strong evidence...

I definitely understand that genetic variants are very important for understanding disease, we’re making the same points there. I guess my concerns all boil down to: this specific individualistic method of pulling out (largely heterozygous) variants by cross-referencing with symptoms of...

Three separate features for three nominally significant pathway hits, which were all listed on the figure itself next to the dot for their respective pathways I agree, it’s a small point to belabor, probably best to leave it here.

^breaks added. *IMID = immune mediated inflammatory disease That's interesting. Confirms what you would expect from previous literature, but this has the added value of doing a robust batch correction across lots of different experiments to allow direct comparison

It's a necessity only if you're trying to prove the relevance of your finding--which doesn't matter here when it's already been made clear that the enrichment was only driven by one single metabolite (and therefore isn't that relevant). It's misleading only for people who don't fully read the...

I think the potential use of this kind of work is not necessarily to understand the fundamental driving biology of anything, but to have a reference source that answers “what do circulating cells actually look like in conditions X Y and Z?” So that if you sample someone’s blood and find a...

you might have to talk to journals about limits on the number and size of figures then (and balancing that with making sure all the text is a readable size)

I really appreciate you continuing to engaging here. I can definitely see the utility from your perspective and understand how your background leads you there. I guess my experience comes from doing a lot of omics analysis myself and seeing first hand how much overfitting and lack of...

But the crucial difference between an individualistic approach and SequenceME is that being able to show a quantitative difference in cases versus controls actually lets you make a conclusion about the relevance of the variant, whereas linking the variant to common symptoms does not (though it...

Maybe, maybe not. I guess coming from environments where perfectionism was expected to the point of paralysis, I have just learned the hard way that if I try to compensate for the many ways that someone barely giving my work the time of day and with little context-specific knowledge might...

Sure but a box/jitter plot will also show distribution. A histogram can show distribution but doesn’t lend itself to adding stats

I think the main value of box plots (and/or jitter plots) is it’s infinitely neater to add brackets for significance especially when doing multiple group comparisons.

I see your point. Usually on my own plots I would have two different colors denoting p<0.05 and adj. p<0.05. I think the line is most often there because the first thing that someone in my field would want to know is whether we're looking at a situation of just a few weak hits that need to be...

@Hutan I completely understand your reasoning and I hope I've made it clear that I wouldn't remotely characterize your comments in this thread as giving people unwarranted grief. I think it's really valuable to have your criticisms (and I was very happy to have your discussion on one of my own...

Yes, most plots like this will include that because you need a way to show where -log10(0.05) is. I agree that perhaps to someone briefly skimming the figures from the paper, this might have the unintentional effect of making it seem like those particular findings are stronger than they are. But...

I'm not sure I agree, the context of PCA usage is really different here and in the Tate paper. For an epigenetic screen, the purpose of showing a PCA as the first step of your analysis is to determine whether your variable of interest represents a strong axis of variation in your data (i.e. one...

This thread might be of interest? I just started reading through it. https://www.s4me.info/threads/glymphatic-clearance-controls-state-dependent-changes-in-brain-lactate-concentration-2017-lundgaard-et-al.47447/#post-657787 I think it's also worthwhile to be specific about what waste management...