A “Metabolic Trap” for Chronic Fatigue Syndrome (ME/CFS)? Send in your genome to help research.

M

Mattie

Senior Member (Voting Rights)
Yet another hypothesis on HealthRising.org

https://www.healthrising.org/blog/2018/04/03/a-metabolic-trap-for-chronic-fatigue-syndrome-me-cfs/

Researcher Robert Phair is seeking ME/CFS patients who have had their genomes sequenced and who would be willing to share their data for research purposes. That includes 23andme data as well.

Edit: Dr. Phair now now has enough 23andMe data but could still use whole exome or whole genome data
Phair got involved in Ron Davis’s work after reading about it in the Stanford Alumni magnazine. Robert Phair had chanced on something that nagged at him. It was a metabolic result in the Severe ME/CFS Patient study that just didn’t make sense to him. Many of us would probably move on to what we did understand, but the disconnect really bugged Phair. As Phair dug deeper into the possible causes of the weird data, a “metabolic trap” – a kind of biological sinkhole – opened up before his eyes. Once the process – which involved amino acid oxidation – started, he saw no way for an ME/CFS patient to get out of it without outside help (e.g. a treatment). Looking further, he and Davis realized it could conceivably explain some fundamental symptoms in ME/CFS.
Since then, he’s been creating model simulations to test his hypothesis. Thus far, he’s created kinetic models of the central metabolic systems in the body (mitochondrial electron transport chain, TCA cycle, fatty acid beta oxidation, amino acid oxidation, glycolysis and pentose phosphate pathway, purine synthesis and degradation, and NAD synthesis).

Using Davis’s genomics data from the Open Medicine Foundation’s Severely Ill Big Data Project, Phair has examined the exons (the part of the DNA which actually codes for proteins) of 100-plus genes involved in energy production. First, a variant commonly found in the general population — but which was more commonly found in ME/CFS — popped up. Digging deeper into the genes encoding NAD synthesis from tryptophan, two more gene variants were found.
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The team will use “tracer” metabolites to determine if the cells with these mutations are, in fact, functioning less effectively. Phair said they should know if the metabolic trap is present in the white blood cells of ME/CFS patients by the end of summer.
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We are seeking CFS/ME patients who have had their genomes sequenced and who would be willing to share their data for research purposes. Your data would help us test theories about gene variants that may have predisposed you to developing CFS/ME when you encountered the infection or other stress that was the cause of your case of CFS/ME. We cannot provide feedback or use the data in studies. Nevertheless, confirmation or refutation of what we find in professionally acquired and processed WGS or exome sequencing data could help us a lot in our search for something that helps every ME/CFS patient.

You can reach me at rphair@integrativebioinformatics.com. I am working on CFS as a volunteer because I have a friend with the disease and another friend whose son is severely ill with CFS. There is no charge for my work on CFS.

Your data would be most comprehensive and powerful in the form of .VCF (Variant Call Format) file but we will work to find a way to analyze your data in any format you are able to provide.

Please also tell us your age and gender and write a paragraph or a page with a description of how you came down with ME/CFS. A list of current symptoms is optional, but desirable.
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Speculative but very interesting (even if it reminds me of the Dynamics & Control module I did years back, *shudder*). I seem to recall another ME/CFS researcher (Klimas?) having a similar proposed mechanism of action and who believed a 'nudge' to the system could lead to a permanent reset. I imagine it also ties in with Naviaux's approach as well.

The proof of the pudding (to me) will be whether said hypothesis could explain PEM, specifically its delayed impact.
 
@Mattie, do you think it would be worth adding to your title, 'Robert Phair seeks data from ME/CFS patients who've had their genomes mapped'?

Personally, I'd like to know more about his project before I sent him anything but anyone who gets Ron Davis's attention is interesting.

Another one for your Q&A list, @Andy?
 
alicec said:
He says specifically that he is looking for whole genome or exome sequences, not 23andme.
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He prefers whole genome, but 23andme data is also useful.

E-mail from Dr. Phair:

Yes, the .txt format will work. 23andMe only covers three of the five genetic variants that are important for the metabolic trap theory, but I can say that even this limited information is useful.

The 23and Me file that I need has a filename like this: genome_firstName_lastName_Full_date_time_in_digits.txt
so if it was mine it would be something like
genome_Robert_Phair_Full_20180315085441.txt
.zip instead of .txt is also fine

If you can open the file in a text editor it should begin with a header that looks like this:
# This data file generated by 23andMe at: Wed Jun 14 12:04:30 2017
#
# This file contains raw genotype data, including data that is not used in 23andMe reports.

Regards,
Robert D Phair PhD | Chief Science Officer | Integrative Bioinformatics Inc
Mountain View, CA

Edit: Dr. Phair now now has enough 23andMe data but could still use whole exome or whole genome data
 
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Mattie said:
Yes, the .txt format will work. 23andMe only covers three of the five genetic variants that are important for the metabolic trap theory, but I can say that even this limited information is useful.
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what are the RSid's for the 3 genetic variants on 23andme?
 
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