A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome, 2021, Fluge, Mella et al

This is cool I have a lot of thoughts about this.

First thing is Hoel 2021 use serum and Germain 2018 use plasma. The metabolomes of serum and plasma differ in a few ways, most relevant here is serum have higher levels of amino acids than plasma. It's not totally clear why this is but it's discussed in this paper and they suggest it could the result of proteolysis in serum or from activated platelets (EDTA/Citrate in plasma prevents this from happening). So it possibly follows that the amino acids between these two papers disagree greatly, despite some large fold changes reported.

Second thing is that in Hoel 2021 the majority of patients and controls are non-fasting. I couldn't see them report in Germain 2018 whether they were fasting or not. I would expect big differences between fasting and non-fasting states. Naviaux's paper and Lipkin/Fiehn's paper for example both have patients in the fasting state so I would not be suprised if there's disagreement between these sets of papers.

Also, are all of these metabolites here reported as significant in both of these papers? If there are metabolites that aren't significant included then you might expect them to be governed by sampling bias/noise and I would not expect these to correlate well between studies necessarily.

Good idea, all for sharing code! Have you tried the package MetaboAnalyst? Might be able to do what you're looking for. It can handle KEGG/CHEMID/ compound names and surely has a function to switch between them.

I Agree! I am a theme_minimal() appreciator.

I think this is a good idea. In multiple metabolomics papers there seem to be big differences between the sexes. In Hanson lab's longitudinal 2 day CPET study the glutamate phenotype they report is almost exclusively a female one.

 

It's interesting to see strong positive agreement about gamma-glutamylated amino acids (glutamate, lysine, tryptophan etc) in @Murph 's comparison. These are amino acids which are attached to a glutamate(mine) at its gamma carbon position. They are made from the enzyme Gamma-glutamyl transferase GGT, which uses Glutathione as a substrate. I made this schematic in the thread on Jason et al 2022's pre illness metabolomics paper highlighting the pathways involved, and gamma-glutamylated amino acids are on this pathway. I've highlighted them in the same schematic in purple:



These pathways are very liver based - I think possibly in the CNS as well. GGT is a marker of liver disease. I'm wondering if there's a nitrogen homeostasis problem.

 

Great work, @Murph and @chillier!

For anyone who doesn't know what nitrogen homeostasis is, here's a bare bones explanation I found on BBC Bitesize (which has replaced the children's library as my go-to resource for anything remotely sciency ):

https://www.bbc.co.uk/bitesize/guides/zxgmfcw/revision/3

 

impaired glycolysis may also impact GGT - so cycles are probably interacting

there has been comment made ( Ron Davis?) that some aspects of ME look like diabetes ( or some forms of cancer which may be another glucose dysregulated condition) - which would make sense if you can't process glucose.
GGT is also indicated in fatty liver disease -the non alcoholic version of which is on the increase and has been suggested that high carb diets are the culprits.
GGT is linked to cardiovascular health too.
Role of Impaired Glycolysis in Perturbations of Amino Acid Metabolism in Diabetes Mellitus - PMC (nih.gov)