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

Sly Saint

Sly Saint

Senior Member (Voting Rights)
See here for the abstract and links to the 2025 ME/CFS paper: link

See here for a link to a 2024 paper on covid-19 outcomes: link
(Development and evaluation of blood-based prognostic biomarkers for COVID disease outcomes using EpiSwitch 3-dimensional genomic regulatory immune-genetic profiling, 2024, Hunter et al)



Oxford BioDynamics(OBD) , a biotechnology company developing precision medicine tests, said its prognostic Covid Severity Test (CST) has been presented in a peer-reviewed paper published in the European Society of Medicine, with extended analysis into the related conditions of Long Covid and Chronic Fatigue Syndrome.

The test makes predictions based on a 6-marker model. In the published study, it demonstrated a high positive predictive value for high-risk disease outcomes in the validation cohort. Within the validation cohort, two patients declared clinically to be mild cases were identified as high risk by the test and subsequently died within 28 days of admission.

The results suggest an early, pre-symptomatic detection by the biomarkers of a hyperinflammatory state leading to fatal outcomes. The test for high-risk disease outcome demonstrated a positive predictive value (PPV) of 92.9%, 88% sensitivity, 87% specificity, and a balanced accuracy of 87.9% for all 116 patients used in the study.

Moreover,

OBD
noted that its EpiSwitch database, on which the test is based, was useful in identifying genes associated with patients suffering from Long Covid and other fatigue conditions such as Chronic Fatigue Syndrome (CFS) and Myalgic Encephalomyelitis (ME), for which the largest risk of onset is associated with infectious diseases.



View from Vox
Oxford BioDynamics shares surge 13% in early Friday trade, as the company announces the publication of a paper in a peer-reviewed journal detailing the effectiveness of its EpiSwitch platform-based Covid Severity Test (CST), with related insight linking it to Long Covid and CFS/ME. The platform has already delivered commercial tests and reliable biomarkers for immuno-oncology (CiRT) and prostate cancer (PSE), now adding Covid and fatigue-related conditions to the list.

Investors have more to look forward to, as the London School of Hygiene and Tropical Medicine, Norwich Medical School, and University of East Anglia, have now agreed to grant OBD access to a biobank of samples from CFS/ME patients for direct analysis and identification of diagnostic and prognostic blood biomarkers.
Click to expand...
Oxford BioDynamics shares gain on Covid test publication, advancing Long Covid and Chronic Fatigue Syndrome research - Vox Markets

(sorry I have looked for the research this is referring to)
 
Last edited by a moderator:
I think this is the paper they mention:

Development and evaluation of blood-based prognostic biomarkers for COVID disease outcomes using EpiSwitch 3-dimensional genomic regulatory immuno-genetic profiling, 2024, Hunter et al

Using the 3D genomics knowledgebase, with >1 billion 3D genomic datapoints derived from clinical studies, a subset of 77 of the acute COVID-associated prognostic 3D biomarkers were found close to 10 loci genetically linked to fatigue-dominant PCS, and to be informative biomarkers in 6 diseases with fatigue as a symptom.
Click to expand...
 
InitialConditions said:
View attachment 23893 View attachment 23894
Click to expand...
Oxford BioDynamics shares surge 13% in early Friday trade, as the company announces the publication of a paper in a peer-reviewed journal detailing the effectiveness of its EpiSwitch platform-based Covid Severity Test (CST), with related insight linking it to Long Covid and CFS/ME.
Click to expand...
Zooming in more, nothing special happened this morning. The stock went up from yesterday, but still lower than two days ago. And the paper above, if it's the right one, was published in September, so I don't know why it would make the stock surge today.

Screenshot_20241025-151250.png
 
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
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; Pchejetski, Dmitri

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.

Link | PDF | Journal of Translational Medicine | Open Access
 
Sly Saint said:
Oxford BioDynamics shares gain on Covid test publication, advancing Long Covid and Chronic Fatigue Syndrome research - Vox Markets

(sorry I have looked for the research this is referring to)
Click to expand...
Paper published with fanfare on blood-based dx test. lots of reasons this could be a whole lot of nothing--penny stock biotech, limitations due to controls, independent replication necessary, "Who?" however, quite promising if validated.

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-07203-w

https://www.thetimes.com/uk/healthcare/article/first-blood-test-chronic-fatigue-syndrome-l7shfd09q

https://www.theguardian.com/society...-test-to-diagnose-chronic-fatigue-syndrome-me

there are a few more tabloid articles plus this which will surprise nobody

"Nothing To See Here: SMC"
 
Last edited by a moderator:
www.theguardian.com

Scientists develop first ‘accurate blood test’ to detect chronic fatigue syndrome

Research could offer hope for ME patients – but some experts urge caution and say more studies needed
www.theguardian.com www.theguardian.com

Prof Chris Ponting, chair of medical bioinformatics at the University of Edinburgh, said some of the claims made by the research team were “premature”.

He said: “This test needs to be fully validated in better-designed and independent studies before it is considered for clinical application. Even if validated, the test will be expensive, likely (about) £1,000.”
Click to expand...
 
I'd love for the company/authors to tell me that I'm wrong, but here is my critique up at everyone's favourite Science Media Centre:

“The authors claim a ‘revolutionary blood test’ for ME/CFS based on a technology, EpiSwitch®, developed by Oxford BioDynamics Plc who co-authored and funded this research. Their proprietary technology infers how often two regions of a chromosome are in spatial proximity within a sample’s cells. This study investigated these “chromosome conformations” in the peripheral blood mononuclear cells from 47 ME/CFS cases and 61 control patients. This technology, they propose, provides blood-based diagnostic biomarkers for ME/CFS and likely explains its pathology.

“Despite the test predicting 22 of 24 cases and 44 of 45 controls in independent samples, these claims are premature. This is because results could be confounded in three ways: by (1) Sex and/or by age: sex- and age-matching was not done (beyond matching age criterion of 20-80 years old); (2) Batch: all cases were from the CureME Biobank, whereas most (41 of 61) controls came from the company’s own biobank; and, (3) Inactivity and severity: all cases had severe symptoms and were house-bound, whereas all controls were healthy and likely physically active.

“This test needs to be fully validated in better designed and independent studies before it is considered for clinical application. Even if validated, the test will be expensive, likely ~ £1,000.”
 
hotblack said:
Thanks for this @Chris Ponting I was just about to share your comments. Looks some we need some caution then. Would be great if we could see this replicated of course.

Did you have any thoughts on the signalling pathways they identified and if this fits in with DecodeME at all?
Click to expand...
I will think about whether their results and DecodeME's are concordant only when the EpiSwitch test is applied to (i) samples from cases and controls when they are taken, and are stored, in exactly the same way, (ii) when they more precisely match for age and sex, (iii) when they include cases of all severities and account for differences due to inactivity, and (iv) when they show that results are not due to any comorbidities among cases/controls.
 
Understood. Thanks @Chris Ponting

@DMissa I’m not sure it is, the tweet says
The 47 ME/CFS samples are "CCC and/or CDC 1994" from the UK ME/CFS Biobank at the London School of Tropical Medicine. The "/or CDC 1994" is problematic as it mixes ME/CFS patients with PEM in with CFS patients without PEM. We don't know how many were CCC and how many were CDC.
Click to expand...
But I cannot see this claim in the paper and the criteria for the UK ME/CFS Biobank are stated as
ME/CFS participants have been diagnosed by physicians and are compliant with CDC ’94 (Fukuda) and Canadian Consensus Criteria (CC).
Click to expand...
We have in the past trusted the Biobank sampling. The other concerns @Chris Ponting raises seem more relevant
 
The deeper problem is that this team do not understand what a diagnostic test is for. There is no point in developing a diagnostic test that correlated 100% with a syndrome. If it does, you know you already had a 100% method of recognising the syndrome so the test is unnecessary.

You may get a near 100% discrimination with barn door cases against barn door normal people with a test that turns out to be useful, but the usefulness is demonstrated by its performance in uncertain cases. And it is only useful in those uncertain cases if it reflects some real biological feature that has prognostic or treatment implications.

It is time people stopped thinking their job is to find a test that correlates perfectly and realise that the test is only useful if it tells us something about the underlying biology. The disease then gets re-classified by its biology and we move forward.
 
Jonathan Edwards said:
It is time people stopped thinking their job is to find a test that correlates perfectly and realise that the test is only useful if it tells us something about the underlying biology. The disease then gets re-classified by its biology and we move forward.
Click to expand...
I agree. But if this does turn out to be accurate it potentially does tell us something doesn’t it? At least that’s what the pathways section of the paper seems to indicate? And why I asked Chris about it, although completely understand his response you can’t blame me for trying :)

Of course it looks like we have small sample size, especially relevant if training a machine learning model, confounding factors as mentioned, and question marks over it being some proprietary tech and a study involving a commercial company….
 
You must log in or register to reply here.
Back
Top Bottom