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Incredible work! Just please take care of your body and don't overdo it. I see the section about increasingly bad injuries. You'll still want your joints to work when you're older.

Yes, interesting. Story from Wikipedia:

Out of curiosity, I looked only at the most significant variant in DecodeME only (20:48914387:T:TA). The model predicts that it has effects on these genes. Positive scores mean the ME/CFS risk allele increases expression. Interestingly, it seems to say it has large effects on almost all genes...

Ok, well I did that. I didn't initially filter to brain - I just had the model do all RNAseq predictions for all tissues, using all the variants with p-value less than 1x10^-7 (342 variants). That resulted in 3,800,412 scores, which are all the combinations of variants-genes-tissues. (It's...

The batch variant scoring tool looks like it'll be useful to test many variants at once: https://www.alphagenomedocs.com/colabs/batch_variant_scoring.html I think the goal is basically looking for variants that produce a large (or small if negatives are possible) quantile or raw score. For...

An LD pattern tells a story in terms of helping identify where the causal SNP is, or helping determine if a phenotype might contain the same causal SNP as another phenotype, but I don't think that's what AlphaGenome is doing. If we knew the specific causal variant in ME/CFS, and gave it that in...

Yeah, I'll need to try to understand this more. It looks interesting, but I'm not exactly sure what it's doing. I think there might be two modes? 1. Check the difference in predicted effect between a single ref and alt allele. 2. Just give a long sequence of DNA and see what the prediction is...

Maybe the plot should be zoomed out more? It's only showing one gene at the moment, but the variant could be affecting something else Edit: I think just a bigger number here: interval=variant_output.reference.rna_seq.interval.resize(2**15),

I haven't tried this yet. Been a bit confused about the docs so far. But maybe its better to test all the significant variants in a locus [edit: at the same time] instead of one? I'd be interested in each locus's variants' predicted effect on the brain.

This protocol seems odd. The control is alfacalcidol, some sort of vitamin D analogue, and the active group is alfacalcidol + vitamin D and guidance on ways to get vitamin D, like sun exposure and exercise: Why is the control a vitamin D analogue if they're testing vitamin D efficacy...

Thanks for the detailed analysis. Should we have a system where some scientists run a study and create data, then they hand it off to people they have no connection to, who analyze it and publish it, somehow with no incentive to embellish results? Though I think the "no incentive" is the tricky...

Gotcha. Can it just be metabolites related to two different systems? As in the metabolites in plasma that change due to exercise being involved in pathways that are unrelated to the pathways that make urine metabolites increase.

Some of the above about how normalization might affect this gets a bit out of my comfort zone, but overall, I think we're basically coming back around to the idea that there may be more variability in deltas in specific metabolites. Exemplified by this amazing illustration: Scenario #1 with...

I think I understand, but it seems to me that this is just what we expect to see all the time. I'll refer to this: If one group gets a true effect intervention, while the other gets the placebo, then the plot of change in steps would look pretty similar to the plots from the study. The code...

I'm a bit confused about what you're trying to show. HC ends up with a significant difference because they do have a difference, while ME/CFS doesn't because they don't. Your plot has equal SDs for one metabolite, and a true difference between groups, so the plot seems like what we'd expect...

Maybe that'd be fine in a paper, but in terms of general discussion of a disease, maybe it's good to be able to place it in a category. "What kind of disease are you studying?" "It's neurological. "Oh, interesting, vascular issues? "No, neuroimmune." People outside the field might not have any...

Would this very brief summary of your thoughts, @Jonathan Edwards, be accurate and maybe clear up some confusion? "If you think you have MCAS or hEDS, and you think telling your doctor might help improve your care, then feel free. If you want to convince others they may have MCAS or hEDS...

This part?: This seems to suggest that it's okay to do this: https://repub.github.io/DLC_statistical_guides/docs/R/repeated-measures-ANOVA.html Maybe emmeans accounts for the non-independence if it's a mixed effects model somehow. Whether it's actually good for this, I don't know. Some...

Oh ok. That's actually reassuring in terms of data privacy if the investigators literally have no way to identify a sample. I assumed the data was anonymized for analysis and for sending to other institutions, but that there would be some sort of master list identifying each sample in a secure...

If there are any sets of at least two siblings with ME/CFS in the DecodeME cohort, then they could potentially just request the DNA samples of healthy family of those people, since they already have the ME/CFS DNA.