Researchers identify key biomarkers for chronic fatigue syndrome

[SWAlexander]

In the latest News: August 11, 2025

Researchers identify key biomarkers for chronic fatigue syndrome​

excerpt:
When cells expire, they leave behind an activity log of sorts: RNA expelled into blood plasma that reveal changes in gene expression, cellular signaling, tissue injury and other biological processes.

Cornell researchers developed machine-learning models that can sift through this cell-free RNA and identify key biomarkers for myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS). The approach could lead to the development of diagnostic testing for a debilitating disease that has proved challenging to confirm in patients because its symptoms can be easily confused with those of other illnesses.

The findings were published Aug. 11 in Proceedings of the National Academy of Sciences. The lead author is Anne Gardella, a doctoral student in biochemistry, molecular and cell biology in the De Vlaminck Lab.

We identified six cell types that were significantly different between ME/CFS cases and controls,” Gardella said. “The topmost elevated cell type in patients is the plasmacytoid dendritic cell. These are immune cells that are involved in producing type 1 interferons, which could indicate an overactive or prolonged antiviral immune response in patients. We also observed differences in monocytes, platelets and other T cell subsets, pointing to broad immune dysregulation in ME/CFS patients”
https://news.cornell.edu/stories/20...ntify-key-biomarkers-chronic-fatigue-syndrome

 

[Mary]

From the study:

The cell-free RNA classifier models had 77% accuracy in detecting ME/CFS – not high enough for a diagnostic test yet, but a substantial leap forward in the field.

I wonder what degree of accuracy is required for a biomarker? And also, the testing might be more accurate than we think, depending on how the patient cohort was identified. The study had 93 persons with ME/CFS and 75 sedentary but healthy controls.

 

[SWAlexander]

I wonder what degree of accuracy is required for a biomarker?

I will wait for Jarred Younger, PhD's, analytical report.
My attempt to study the ME/CFS genetic components ended after 10 hours due to severe headaches, forcing me to stop.

Matching chromosome position manually and p-value from this plot with SNP database entries.

Example: “G protein-coupled receptors (GPCRs)” (don’t try to study unless you have one year to read and compare)

RABGAP1L: Search results - Items: 1 to 20 of 6500

Biochemistry, G Protein Coupled Receptors: https://www.ncbi.nlm.nih.gov/snp/?term=BTN2A2

This is a Manhattan plot from a genome-wide association study (GWAS), which shows genetic loci along the chromosomes (x-axis) and their significance levels (y-axis, as –log₁₀ p).

The genes labeled here — RABGAP1L, BTN2A2, FBXL4, SUDS3, OLFM4, CCPG1, CA10, and ARFGEF2/CSE1L — likely correspond to lead SNPs with associated rsIDs.

To find the exact rs numbers (e.g., rs123456), you would need to:
Check the original GWAS paper or supplementary tables — they typically list the top SNPs (with rsIDs, chromosome positions, and p-values).

Use GWAS Catalog or dbSNP — search each gene name along with “GWAS” to locate the specific SNP(s) identified.

Matching chromosome position and p-value from this plot with SNP database entries.

Example: “G protein-coupled receptors (GPCRs)” (don’t try to study unless you have one year to read and compare)

After :
RABGAP1L: Search results - Items: 1 to 20 of 6500 --- I gave up
Biochemistry, G Protein Coupled Receptors: https://www.ncbi.nlm.nih.gov/snp/?term=BTN2A2

 

[BrightCandle]

From the study:



I wonder what degree of accuracy is required for a biomarker? And also, the testing might be more accurate than we think, depending on how the patient cohort was identified. The study had 93 persons with ME/CFS and 75 sedentary but healthy controls.

Realistically about 95% and rejection of other other conditions that are often misdiagnosed such as anxiety, depression and MS. To be a biomarker it also has to correlate with the severity of the disease, so it has to map to mild/moderate/severe. The only test I know of that has met this was the nanoneedle test on salt challenged cells.

 

[SWAlexander]

nanoneedle test on salt challenged cells

I'm glad you addressed what is rarely mentioned.
Yes, sodium stress can alter cellular energy metabolism.

From a cause-and-effect perspective, measuring high or low sodium levels alone does not identify the underlying cause of the imbalance. Moreover, it is important to determine whether sodium deficiency affects only muscle cells or also impacts neural tissues, such as those of the brain and its protective membranes (meninges).

Over the past two months, I have conducted a self-observation trial by increasing my dietary sodium intake through consumption of pretzel sticks (Brezeln) prepared with added high food grade natrium before baking. The observed outcome was a reduction or balance in apparent aldosterone activity, as indicated by decreased urinary frequency and more energy.

The open question is how variations in sodium concentration affect electrical conductivity in both blood and muscle tissue, and whether similar effects occur in neural tissue, including the brain. This encompasses evaluating sodium’s role in action potential generation, signal transmission, and excitability in muscle fibers and neurons, as well as its influence on overall tissue conductivity.

Before SARS-CoV-2 infection, laboratory tests from 2020 indicated that serum sodium levels were within the normal reference range. Following the infection, laboratory results from 2022 demonstrated hyponatremia (serum sodium below the normal range).

So, I started to investigate salt back in 2023:
Sodium and Bicarbonate Deficiency: Understanding Electrolyte Imbalance and Metabolic Acidosis
https://swaresearch.blogspot.com/2025/06/sodium-and-bicarbonate-deficiency.html

The Vital Role of Sodium in Human Health: Balancing Functions, Risks, and Interactions
https://swaresearch.blogspot.com/2025/06/the-vital-role-of-sodium-in-human-body.html

​

 

[joshualevy]

I wonder what degree of accuracy is required for a biomarker?

The rule of thumb that I remember is that research becomes interesting at the 80%/80% level. That is no where near high enough to actually use, but it is the place that attracts more research; where research is considered interesting or worthwhile. The first 80% refers to 80% of the people who have the disease have the biomarker, the second 80% refers to 80% of the people who do not have the disease, do not have the biomarker.

Actual use depends on cost of test, impact of use, and many other complex, real world issues. (At extreme: If there is no treatment, there is no cost effective test, because the test doesn't help you. If the treatment is free, then again no test is cost effective because you just treat everyone. If the test is free, then everyone gets it. If the test is fatal no one gets it, etc.) I think for something like ME/CFS (or long-COVID) you are going to need 98% at least, and probably over 99.5%.

Obviously, 77% (seen here) is below, but close, to the lower standard, but not near the higher one.

Of course, that "rule of thumb" dates from the 1800s (maybe even the 1700s) and I'm not sure how computer learning algorithms effect it. It might make it higher or lower.

And also, the testing might be more accurate than we think, depending on how the patient cohort was identified. The study had 93 persons with ME/CFS and 75 sedentary but healthy controls.

True, but the testing might be less accurate than we think. In real life (in real research?) both happen.

 

[joshualevy]

To be a biomarker it also has to correlate with the severity of the disease, so it has to map to mild/moderate/severe.

Disagree. A biomarker which is just yes/no for the disease would be incredibly valuable. A biomarker that correlated with severity would be more valuable, of course. But a yes/no biomarker is a biomarker. It would lead to a better world than we have now.

 

[SWAlexander]

At extreme: If there is no treatment, there is no cost effective test, because the test doesn't help you.

How long will it take? Meanwhile, people continue to suffer.

Even if there’s no established treatment, science—and medical professionals—can still take action. By comparing related symptoms with existing scientific data, clinicians can request targeted blood tests, identify patterns, and deepen our understanding of the condition.