Beyond Linear DNA: Unlocking the Mystery of ME/CFS Through 3D Genomics

Last updated: 05 Aug 2026

I recently appeared on the Finding Genius Podcast with Professor Dmitry Pshezhetskiy, where we discussed the development of a revolutionary blood test for Myalgic Encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS). It was a fascinating conversation that allowed me to explain some complex science in accessible terms, and I wanted to share some of those insights here.

For decades, millions of people living with ME/CFS have faced the same frustrating experience: they feel profoundly unwell, yet every blood test comes back normal. They have nothing to show for it. They look normal, their bloodwork is normal, and yet they feel anything but. This diagnostic void has left patients in limbo, often for years, while clinicians struggle without objective tools to confirm what patients already know about their own bodies.

But what if we've simply been looking at the wrong level of biology?

The missing dimension

Traditional blood tests examine individual markers — proteins, antibodies, metabolites — searching for a single smoking gun. But ME/CFS doesn't work that way. It's a complex, multi-system condition affecting energy production, immune function, and neurological processes simultaneously. Looking for one deranged marker is like trying to understand a symphony by listening to a single instrument.

At Oxford BioDynamics, we've spent 20 years developing EpiSwitch® technology that captures something fundamentally different: the three-dimensional architecture of the genome itself. This isn't about which genes you have; it's about how your genome is physically organised and regulated within living cells.

Think of DNA not as a simple string of code, but as an intricately folded structure where distant regions can be brought together to coordinate gene activity. This 3D organisation acts as a master control system, integrating signals from across the genome into stable, reproducible patterns. When something goes wrong systemically, this architecture shifts, and we can detect that shift.

A robust molecular fingerprint emerges

When we applied our EpiSwitch platform to ME/CFS, something remarkable happened. Instead of the scattered, noisy signals that have plagued previous biomarker efforts, we found a coherent molecular fingerprint: 200 specific chromosome conformations that consistently distinguish patients with severe ME/CFS from healthy individuals time and time again.

In our proof-of-concept study, this signature achieved 92% sensitivity and 98% specificity, with an overall accuracy of 96%. For patients who have waited years for validation, these numbers represent something profound: objective, measurable evidence of their condition. This work was led by Oxford BioDynamics in collaboration with the University of East Anglia (UEA), the London School of Hygiene & Tropical Medicine, and Royal Cornwall Hospitals NHS Trust, and is published in the peer-reviewed Journal of Translational Medicine [1].

But perhaps more exciting than the diagnostic accuracy is what this fingerprint reveals about the disease itself. When we mapped which biological pathways these 200 markers connect to, they didn't scatter randomly. Instead, they formed a tightly interconnected network touching mitochondrial function, immune signalling, stress responses, and neuroinflammation. These are precisely the systems clinicians have long suspected are involved.

Not one disease, but one network

Our analysis revealed something that may help resolve long-standing debates about whether ME/CFS is truly a single condition. While the specific genes involved vary between patients, they converge on shared regulatory networks. It's like different roads leading to the same destination.

Even more intriguingly, when we compared the ME/CFS molecular landscape with Long COVID and post-traumatic stress disorder — two conditions with reported overlapping features — we found substantial network interconnection despite relatively little direct gene overlap. This suggests these conditions may represent different perturbations of common underlying regulatory systems, potentially explaining why certain triggers can lead to similar clinical pictures.

From diagnosis to treatment

A diagnostic test alone would be transformative for ME/CFS patients; but our technology also points toward therapeutic possibilities. By identifying the central "hubs" within these deregulated networks, we can predict which existing drugs might help restore normal function.

One compelling example is mTOR, a master regulator of cellular metabolism that our analysis flagged as a key network hub. Intriguingly, early investigational work on low-dose rapamycin, an mTOR inhibitor, has been encouraging in small pilot studies. Though it is not yet an approved treatment for ME/CFS, it has shown promise, with response rates around 74% in certain patient subgroups [2]. Our platform may eventually help identify which patients are most likely to benefit from such targeted approaches.

What Comes Next

We're now preparing for the EMERGE trial: a prospective study across seven NHS sites that will test our biomarker in 840 participants, including patients with varying ME/CFS severity, Long COVID, multiple sclerosis (MS), and rheumatological conditions. This will determine whether our test can reliably distinguish ME/CFS from conditions that can clinically mimic it.

For the millions worldwide living with ME/CFS, the message is clear: your illness is real, and science is finally building the practical tools to measure it. The genome's hidden architecture is revealing what standard tests have missed, and with it, a new hope for diagnosis, understanding, and ultimately, treatment.

Dr Alexandre Akoulitchev is Chief Scientific Officer and co-founder of Oxford BioDynamics plc, where he leads development of the EpiSwitch® 3D genomics platform.

Listen to the podcast on the Finding Genius Podcast website here, on Apple here, or watch it on YouTube below.

Sources:

1) Hunter, E., Alshaker, H., Bundock, O. et al. Development and validation of blood-based diagnostic biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using EpiSwitch® 3-dimensional genomic regulatory immuno-genetic profiling. J Transl Med 23, 1048 (2025). https://doi.org/10.1186/s12967-025-07203-w

2) Ruan, B.T., Bulbule, S., Gile, B. et al. Low-dose rapamycin alleviates clinical symptoms of fatigue and PEM in ME/CFS patients via improvement of autophagy: a pilot study. J Transl Med 23, 1148 (2025). https://doi.org/10.1186/s12967-025-07213-8