SequenceME genetic study - from Oxford Nanopore Technologies, the University of Edinburgh and Action for ME

SequenceME: first of a kind genetic study
December 16, 2024

A groundbreaking partnership has launched today.

The partners are working together to secure funding for a study which will analyse the entire genetic code of up to 17,000 people with Myalgic Encephalomyelitis (ME) in a bid to uncover the genetic causes of the illness.

SequenceME will bring together experts from Oxford Nanopore Technologies, the University of Edinburgh and Action for ME, to uncover the root causes of ME and to determine whether ME is one illness, or an umbrella condition encapsulating multiple diseases, such as long Covid and other chronic conditions.

The research team will use advanced whole genome sequencing technology to look at every location in the 3 billion letter genome, enabling the identification of rare genetic variants – small changes to DNA sequence – and structural variations.

This detailed picture will allow researchers to search for the biological causes of ME with unprecedented precision, laying the foundations for breakthroughs in diagnosis and treatment.

The insights from SequenceME would therefore mark a turning point not only for ME but also for conditions like long Covid and other post-viral syndromes. By advancing understanding of this complex and debilitating illness, the study has the potential to deliver profound health, social, and economic benefits, from reducing the strain on healthcare systems to empowering patients with personalised treatments and plans.

The project builds on the DecodeME study, the world’s largest genetic study of ME led by the University of Edinburgh and Action for ME, which investigated whether common genetic variants were more likely to appear in those with ME than those without the condition.

Over 17,000 participants who donated saliva samples to DecodeME have consented to further analysis and he SequenceME partners will seek to analyse them all.

Subject to funding, SequenceME would be the largest global single-disease ‘long read’ genetics study, which gives richer, clearer data, as well as the first in ME to use Oxford Nanopore’s new generation of nanopore-based technology.

The collaboration is supported by Edinburgh Innovations, the University of Edinburgh’s commercialisation service.

Dr Gordon Sanghera, CEO of Oxford Nanopore Technologies, said:

"DecodeME created the world’s largest ME/CFS study, and we are proud to take the next step with SequenceME. Using Oxford Nanopore’s any-length read sequencing technology, this project will uncover genetic insights that could transform patient care and open the door to personalised medicine for those living with ME.”

SequenceME will prioritise the voices of those most affected. Sonya Chowdhury, CEO of Action for ME, explained:

"This collaboration will place people with lived experience of ME at its heart. The study will focus in its initial phase on severe and very severe cases of ME, ensuring that the people who live with its most devastating impacts are central to advancing understanding and driving meaningful change."

SequenceME presents a unique opportunity for strategic investment in chronic disease research, and the study’s potential to improve outcomes for individuals cannot be understated. This quarter, the study partners concluded a successful pilot phase by completing any-length sequencing of ten individual samples from the DecodeME library, demonstrating the high accuracy and scalability of the study method. The next phase, involving sequencing of 10,000 participants, requires £7 million in funding.

Professor Chris Ponting, DecodeME’s lead investigator at the University of Edinburgh, has urged stakeholders to seize this opportunity saying:

"The SequenceME study represents a unique opportunity to build on DecodeME’s foundation and use world-class technology to address one of the most challenging medical puzzles of our time."

With its ambitious goals and commitment to putting patients at the centre, SequenceME represents a crucial and much needed step forward in understanding and addressing ME.

https://www.actionforme.org.uk/news/sequenceme/

 

wow, sounds like amazing news!

 

Wow, that’s the first time I’ve ever heard that. It’s really refreshing compared to the studies that just ignore anyone who is too severe to make it to the testing center or whatever.

 

The Open Medicine Foundation did a study on the severely ill some years ago, led by Ron Davis, with the idea that the severely ill would provide the strongest 'disease signal'. The 2021 paper linked to there didn't include genetic results (I think) and I couldn't see how many patients were included, though I only briefly skimmed it.

 

It sounds like a really exciting project. Let's hope they can raise the funding!

 

This has got to be massively expensive no? Isn’t Whole Genome Sequencing far more tedious and expensive than GWAS?

 

I think it says they're looking to raise £7,000,000 (seven million pounds sterling), in the article.

 

Wow. They must have a good chunk of that part funded to be in a position to announce it publicly. So very exciting!

 

Right on cue, a preprint came out today that spells out the benefits of applying both GWAS and Whole Genome Sequencing: https://www.biorxiv.org/content/10.1101/2024.12.12.628073v1.full.pdf
“GWAS and LoF burden [whole genome sequencing] tests reveal distinct but complementary aspects of trait biology, with important implications for interpreting and using association studies.”

 

That's pretty awesome.

 

Would be interesting to know the projected timescale for this study.

 

That's not a huge amount for research.

Especially when you consider it'll be possible to use some of the anonymised data for many years to come, pursuing questions not even thought of yet. On one level it's an ME/CFS project, but it's also an investment in very significant library of information.

 

ok - great! That's good to know... I don't know anything at all about this kind of thing

 

Really good news. I hope it starts ASAP. Thanks to all involved. Do we know who is leading the SequenceME collaboration?

Relative to the disease burden and spending on research into other conditions, £7 million is not a lot of money. If the MRC, NIHR or other funding bodies were to reject grant applications for this it would raise serious questions.

 

I see Chris Ponting shared this on Twitter last month:

Oxford Nanopore announces landmark UK Government partnership to advance genomics-driven healthcare innovation in the UK
https://nanoporetech.com/news/oxfor...nomics-driven-healthcare-innovation-in-the-uk

 

Unfortunately due the lack of funding being raised privately for ME/CFS in comparison to some other conditions, I don’t see £7 million being raised if the MRC, etc. don’t fund it.

It’s great to have people and also a charity willing to put in the work to put together an application.

 

I don't really!

But as well as the potential for progress on intractable chronic illnesses, there's a big economic incentive. The history of the PACE trial suggests that chiming with strong political priorities doesn't do any harm to the prospects of a team with a persuasive idea, and with inflation factored in PACE probably cost more than this.

[Edited for clarity]

 

Thank you, Chris.

What is the situation in regards to funding?

I am not sure what is the situation post Brexit, but could you apply for EU funding for this project?

I vaguely remember reading something about how Starmer (?) wants to reestablish eligibility for UK based projects for HORIZON (?) funding?

 

JK Rowling lives in Edinburgh maybe she would like to contribute?