Tools
Tools
Hunter, Ewan, Alshaker, Heba, Bundock, Oliver, Weston, Cicely, Bautista, Shekinah, Gebregzabhar, Abel, Virdi, Anya, Croxford, Joseph, Dring, Ann, Powell, Ryan, Vugrinec, Dominik, Kingdon, Caroline, Wilson, Carol, Dowrick, Sarah, Green, Jayne, Akoulitchev, Alexandre and Pchejetski, Dmitri 
ORCID: https://orcid.org/0000-0003-1074-9261
(2025)
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.
Journal of Translational Medicine, 23 (1).
ISSN 1479-5876
Preview |
PDF (s12967-025-07203-w)
- Published Version
Available under License Creative Commons Attribution. Download (4MB) | Preview |
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating, multifactorial disorder characterised by profound fatigue, post-exertional malaise, cognitive impairments, and autonomic dysfunction. Despite its significant impact on quality of life, ME/CFS lacks definitive diagnostic biomarkers, complicating diagnosis and management. Recent evidence highlights potential blood tests for ME/CFS biomarkers in immunological, genetic, metabolic, and bioenergetic domains. Chromosome conformations (CCs) are potent epigenetic regulators of gene expression and cross-tissue exosome signalling. We have previously developed an epigenetic assay, EpiSwitch®, that employs an algorithm-based CCs analysis. Using EpiSwitch® technology, we have shown the presence of disease-specific CCs in peripheral blood mononuclear cells (PBMCs) of patients with amyotrophic lateral sclerosis (ALS), rheumatoid arthritis (RA), prostate and colorectal cancers, diffuse Large B-cell lymphoma and severe COVID-19. In a recent paper, we have identified a profile of systemic chromosome conformations in cancer patients reflective of the predisposition to respond to immune checkpoint inhibitors, PD-1/PD-L1 antagonists, with 85% accuracy. In this Retrospective case/control study (EPI-ME, Epigenetic Profiling Investigation in Myalgic Encephalomyelitis), we used whole blood samples retrospectively collected from n = 47 patients with severe ME/CFS and n = 61 age-matched healthy control patients to perform whole-genome 3D DNA screening for CCs correlating to ME/CFS diagnosis. We identified a 200-marker model for ME/CFS diagnosis (Episwitch®CFS test). First testing on the retrospective independent validation cohort demonstrated a strong systemic ME/CFS signal with a sensitivity of 92% and a specificity of 98%.Pathways analysis revealed several likely contributors to the pathology of ME/CFS, including interleukins, TNFα, neuroinflammatory pathways, toll-like receptor signalling and JAK/STAT. Comparison with pathways involved in the action of Rituximab and glatiramer acetate (Copaxone) (therapies with potential in ME/CFS treatment) identified IL2 as a shared pathway with clear patient clustering, indicating a possibility of a potential responder group for targeted treatment.
| Item Type: | Article |
|---|---|
| Additional Information: | Data Availability: Knowledge graphs were generated using the EpiSwitch 3D-Genomics large language model (LLM), which employs a unique embedding approach. This platform integrates advanced semantic parsing with over 1.5 billion experimentally-verified 3D genome interactions. Leveraging proprietary AI models trained on chromatin architecture, it enables mapping of regulatory circuitry, identification of causal mechanisms, and prediction of the effects of non-coding and structural variants within their native 3D genomic context. These tools are deployed on Google Cloud in collaboration with Google. Data is available on request https://www.oxfordbiodynamics.com/contact-us#contact-us-form-wrapper. |
| Uncontrolled Keywords: | 3d-genomic profiling,autonomic dysregulation,blood test,blood-based biomarkers,chromosome conformations,chronic fatigue syndrome,diagnosis,epigenetics,cfs,myalgic encephalomyelitis,general medicine,general biochemistry,genetics and molecular biology,sdg 3 - good health and well-being,das in place,contact-us#contact-us-form-wrapper.,2026 ,/dk/atira/pure/subjectarea/asjc/2700/2700 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 10 Nov 2026 11:13 |
| Last Modified: | 10 Nov 2026 11:13 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/105039 |
| DOI: | 10.1186/s12967-025-07203-w |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |