Visualize the Invisible Illness: 96% Expectation, Certainty to Follow - Distinguishing Chronic Fatigue Syndrome with "3D Genome"

What the News of "96% Accuracy" Means

A UK research team has suggested the possibility of diagnosing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) through a blood test—such headlines have been circulating in European media and on social networks. The origin was a report by The Independent on a "blood test with 96% accuracy." The article, reprinted from a contribution to The Conversation, organizes the key points and limitations of the research, as well as its implications for patients.The Independent

The research itself is at the proof-of-concept stage. The subjects were 47 patients with severe ME/CFS and 61 healthy controls. Approximately 200 biomarkers derived from **epigenetics (3D genome structure/chromatin folding) were extracted from the blood, and it was reported that patients and healthy individuals could be distinguished with a sensitivity of 92% and specificity of 98%. The overall diagnostic accuracy reached 96%**.BioMed Central

Why Diagnosis Has Been Difficult Until Now

ME/CFS is characterized by severe fatigue that does not improve with rest and post-exertional malaise (PEM), where symptoms worsen with minimal exertion, but symptoms vary widely, including headaches, joint pain, sleep disorders, orthostatic intolerance, and cognitive decline. Due to the lack of definitive tests, diagnosis has relied on clinical criteria application plus exclusion diagnosis, and it is not uncommon for confirmation to take several years. As early rest may influence long-term outcomes, delayed diagnosis can lead to decreased recovery rates and increased risk of severity—this background has heightened expectations for the "emergence of a test."The Independent

The Content of the Research: The Key is "3D Genome"

The test focuses not on the genes themselves but on the three-dimensional folding patterns of DNA (chromosome conformation). It captures epigenetic wiring that changes with environmental stress, infection, or exercise, aiming to find an "ME/CFS-specific signature." The paper suggests clusters related to the IL-2 pathway of immune signaling, with clear separation between patient and control groups.BioMed Central

This technology involves the platform (EpiSwitch) of the UK company Oxford Biodynamics (OBD), established through academic and industrial collaboration. However, how this corporate involvement affects conflict of interest and the evaluation of versatility needs to be rigorously assessed through external independent verification.sciencemediacentre.org

How to Interpret "96%": Expectations and Reservations

The impactful number fueled the spread of news, but careful interpretation is needed. First, the sample size is small (47 patients, 61 controls), the patients are mostly severe, homebound, or bedridden, and differences in gender ratio and activity levels could affect biomarkers.The Independent

Additionally, UK media included estimates like "estimated cost is about £1,000" and expert opinions that further large-scale verification is essential for clinical implementation. Verification of mild to moderate cases and differentiation from similar symptoms (fibromyalgia, multiple sclerosis, etc.), as well as discrimination performance, including diversity of race, age, and underlying conditions, are listed as challenges.The Guardian

The UK Science Media Centre also emphasized the importance of methodological characteristics, considering that "the company is a co-author and funder" and "the samples are 3D structure estimates derived from PBMC (peripheral blood mononuclear cells)," highlighting the need for independent verification and reproducibility.sciencemediacentre.org

The Atmosphere on Social Media: Hope, Caution, and Implementation Cost

On social media, generally, three moods intersected.

1. Hope Among Patients and Stakeholders
   Many welcomed it as a shift from long-standing "invisibility." There is hope that having a diagnostic "yardstick" will advance discussions on medical access, welfare benefits, and work accommodations. On X (formerly Twitter), posts explaining key points like "a test using DNA folding could help over 400,000 patients in the UK" spread widely.X (formerly Twitter)

2. Caution from Researchers and Clinicians
   In Reddit's medical communities, posts pointing out concerns like "small discovery cohort and lack of independent validation set" sparked discussions, with mentions of "concerns of overfitting." In one thread, critiques like "96% accuracy is a textbook sign of overfitting" and "insufficient independence of validation samples" were raised, with many calling for external data retesting.Reddit
   Meanwhile, in the Long-COVID community, there were balanced evaluations like "solid proof of concept, but due to corporate funding, small scale, and homogeneous data, healthy skepticism is needed."Reddit

3. Realistic Views on Implementation (Price and Access)
   Clinical implementation faces barriers of price and test logistics. UK papers indicated an estimate of about £1,000 per test, reporting that handling in insurance reimbursement and national healthcare (NHS) will be key. Patient organizations also call for policy dialogue to balance usefulness and fairness.The Guardian
   
   

The Social Impact of "Accelerated Diagnosis"

ME/CFS is a condition where pacing to avoid post-exertional malaise (PEM) and consideration in lifestyle, work, and education design is crucial. If objective testing is introduced,

• Early diagnosis → Early lifestyle adjustments and support measures

• Visualization of the disease → Mitigation of prejudice and denial

• Homogenization of research subjects → Acceleration of treatment development
  such virtuous cycles are expected. Especially as the connection with Long-COVID is also discussed, there is significant potential for advancing a cross-sectional understanding of immunity, inflammation, and metabolism.The Independent

The Remaining Question: What Defines "ME/CFS-ness"?

ME/CFS is more of a syndrome than a single disease, with significant diversity in pathology. The signature found in this study was identified mainly in severe cases, and it is unclear how generalizable it is to patients with mild to moderate cases or those with comorbidities. Furthermore, the differential performance with diseases that have overlapping symptoms, such as fibromyalgia and autonomic dysfunction (POTS), must also be examined. These will only become clear through multicenter, prospective studies by external teams.The Independent

Next Steps: Reproducibility, Comparison, and Cost

For future implementation, at least the following three points will be the focus.

• Reproducibility: Can the same accuracy be achieved in multinational, multicenter, prospective designs? Does it withstand differences in patient demographics (age, gender, disease stage) and blood collection conditions?sciencemediacentre.org

• Comparative Verification: Verify specificity in other disease cohorts (fibromyalgia, MS, autoimmune diseases, etc.). Simultaneously, integratively evaluate with existing candidate biomarkers (immune, metabolic, mitochondrial functions, etc.).The Independent

• Cost and Access: Ensure ##HTML