Development and validation of blood-based diagnostic biomarkers for [ME/CFS] using EpiSwitch®… 2025, Hunter et al. (Oxford Biodynamics)

[duncan]

Are there examples of good diagnostic tests for other aquired syndromes? I get what Jonathan is saying about not having a 'ground truth', but I can certainly see a scenario where a clinical test could be part of diagnosis.

Andersen-Tawil Syndrome, a channelopathy, is confirmed by testing for the KCNJ2 genetic marker.

ATS has several clinical features that are fairly hard to miss, but they are missed regularly by competent physicians, and at the expense of the patient. Why? Probabilities. Clinicians are taught that ATS is exceedingly rare; most believe that there's little chance a case will fall under their lamp.

Thank God for the biomarker test. Validation can come at several different levels. Certainly for both the patient and the clinician. But also for planning purposes if a syndrome is inheritable - which ATS is. The test impacts the patient and the patient's children, and their children.

 

[Jonathan Edwards]

Andersen-Tawil Syndrome, a channelopathy, is confirmed by testing for the KCNJ2 genetic marker.

Again, ATS is no longer a syndrome. It is now defined as a channelopathy. The test presumably indicates the biological basis of the channelopathy.

If you have no idea what the biological basis for a syndrome is, or whether there are six, the situation is different. Nobody is questioning the value of tests that document a biological abnormality that you can attribute symptoms to.

 

[duncan]

Again, ATS is no longer a syndrome. It is now defined as a channelopathy. The test presumably indicates the biological basis of the channelopathy.

If you have no idea what the biological basis for a syndrome is, or whether there are six, the situation is different. Nobody is questioning the value of tests that document a biological abnormality that you can attribute symptoms to.

I appreciate the point you are trying to make, but I'm not sure how it applies in the real world. Even though the KCNJ2 gene mutation and its relation to ATS were discovered back around 2000, and even though ATS is indeed a channelopathy, it is nevertheless still referred to as a syndrome, and even at times by its old name of a form of periodic paralysis.

Moreover, my understanding is that now there are TWO forms of ATS recognized - ATS1 and ATS2 - where the former is confirmed through the KCNJ2 marker, and the latter through clinical presentation only (i.e. absence of genetic marker).

 

[rvallee]

This study doesn't warrant all this media attention. Wonder if the SMC is to blame for pushing this?

In some way, though, I think it probably answers a very valid question in a recent thread about how will people even know if there is a scientific breakthrough paving the way to a solution.

Probably a similar reason why fraudulent claims of psychobehavioral therapies improving outcomes get so gullibly parroted as fact: there is a deep hunger for answers here. Any answers. Even fake ones. So far, especially fake ones. But one thing there isn't as far as figuring out the cause and producing a solution is indifference to a real solution, it will not go ignored. We'll know if something big hits the moment it's public.

I am obviously biased in favor of what it would mean for us, but I'm fairly sure anything that figures us out will be a sort of skeleton key to open up all sorts of blocked paths all over medicine. It is one of the hardest problem the discipline faces, and other than PEM, I very much doubt that it wouldn't explain all sorts of similar but unrelated things.

 

[Dolphin]

Adam D.
First proposed blood test for chronic fatigue syndrome: what scientists think.
Nature. 2025 Oct 9.
https://www.nature.com/articles/d41586-025-03299-8

 

[John Mac]

Can a new blood test really detect ME/CFS? An expert unpacks new research

Diagnosis for myalgic encephalomyelitis/chronic fatigue syndrome currently relies on sometimes controversial diagnostic criteria – and can take years.

theconversation.com

'Scientists in the United Kingdom say they have developed a blood test that can diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with 96% accuracy – the first of its kind.'

---

'The researchers examined blood samples from people they knew had ME/CFS and identified around 200 such biomarkers. These changes formed a distinct biological “signature” that was not present in the blood of healthy participants in the comparison group.

This signature was very accurate in correctly identifying which samples were from people with the condition and which were from the comparison group.'

---

'However, there were several limitations. The study involved a relatively small number of people: 47 participants with severe ME/CFS and 61 in the healthy “control” group.

The ME/CFS group had more females, and its participants were so severely affected they were housebound. So they presumably had lower activity levels than the control group.

We know a person’s sex and activity levels can influence these chromosomal changes, so this may have affected the results.'

 

[Simon M]

An interesting comment on BlueSky:

I had a look into some. Ingredients:
* a low number P of patients
* a huge list on N parameters
* ignoring the minimum requirement P > 2^N
or N < lb(P)
* i.e. low variability

Mathematically it‘s like investigating young males, projecting on older males AND femals … it won’t work. Chasing winds …

 

[wastwater]

First-Ever Chronic Fatigue Syndrome Blood Test Achieves 96% Accuracy

After years of being told their crushing exhaustion might be “all in their head,” people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome may finally have something they’ve desperately needed: a blood test that proves their illness is real.

studyfinds.org

In A Nutshell​

• A 3D-DNA blood test (EpiSwitch CFS) identified ME/CFS with about 96% accuracy in a small validation study.
• The strongest signals involve IL-2 and other immune-signaling pathways, hinting at biological subtypes.
• The test builds on an existing lab platform used for cancer diagnostics but remains experimental.
• Larger, multi-center studies and independent replication are needed before clinical adoption.

 

[arnoble]

Quite apart from all the important (and valid) study-design and statistical issues raised above, the comment that really stands out for me is:

Looking at the methodology, this seems like exactly the same information that a Hi-C assay would be able to give you, but even less so since it’s only looking at chromosome “loops” and not general structural proximity. I had a chance to attend a lecture on Hi-C a few months ago by someone who has put out a lot of studies since the technology was developed, and it was one of the first times I’ve heard a scientist admit that the last decade of work with their method of choice has by and large failed to deliver on the promised insights. I can’t imagine that proprietary Hi-C Lite would do much better.

The media hype is staggeringly inappropriate.

 

[Kalliope]

Per Fink has his own take on things as usual and says in this Danish article about the study:

"It's exiting if a biomarker for CFS/ME and thus for a functional disorder has been found. But it will require more well-conducted studies to be able to conclude this".

Sundhedspolitisk Tidsskrift Ny britisk test hævdes at kunne diagnosticere kronisk træthedssyndrom - men eksperter advarer
google translation New British test claims to diagnose chronic fatigue syndrome - but experts warn

ETA: The article also quotes Charles Shepherd and Chris Ponting, but makes it sound as if they agree with Fink by writing: "Other experts share Per Fink's cautious approach".

 

[arnoble]

Knowing nothing about 3d-genomics (and being a non-scientist), I found this YouTube resource really helpful and easy to follow:

 

[V.R.T.]

Every time someone does this it plays into BPS hands!

Can't researchers understand that by constantly announcing they have found a biomarker based on premature and in this case poorly conducted findings it delegitamises them AND us in the eyes of the medical establishment.

 

[Utsikt]

Per Fink has his own take on things as usual and says in this Danish article about the study:

"It's exiting if a biomarker for CFS/ME and thus for a functional disorder has been found. But it will require more well-conducted studies to be able to conclude this".

Sundhedspolitisk Tidsskrift Ny britisk test hævdes at kunne diagnosticere kronisk træthedssyndrom - men eksperter advarer
google translation New British test claims to diagnose chronic fatigue syndrome - but experts warn

ETA: The article also quotes Charles Shepherd and Chris Ponting, but makes it sound as if they agree with Fink by writing: "Other experts share Per Fink's cautious approach".

@Chris Ponting tagging in case you feel like Fink is not giving an accurate representation of your statements..

 

[jnmaciuch]

Quite apart from all the important (and valid) study-design and statistical issues raised above, the comment that really stands out for me is:

The media hype is staggeringly inappropriate.

To be fair, this was just the opinion of one person, others would probably disagree. I do think epigenetic and chromatin structure assays can yield useful results, especially when used with a particular hypothesis in mind or by a group that can probe deeper from the results of a screen. But the point this person was making was that Hi-C (and similar methods) are specific examples of a technology that was really hyped up, but its results have been largely less interpretable and actionable than something like single cell RNA-seq or even ATAC-seq