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

Dolphin said:
From what I can see, the amount charities and similar give to medical research in the UK overall is similar if not a bit more than government sources like the MRC, NIHR, etc.

The problem here is the size of the funding being sought (£7 million) is not the sort of money UK ME/CFS charities are raising or likely to raise any time soon (Peter White says Parkinson’s Disease and Multiple Sclerosis charities raise twenty times the amount that UK ME/CFS charities raise (per patient?) so for another condition it might be feasible).
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Just to clarify that I was talking about medical research overall rather than just for ME.

The Association of Medical Research Charities say their members spend £1.7 billion a year on research in the UK. And lots of charities that support research aren’t members (last time I checked none of the UK ME charities were members).
 
Andy said:
I've not been involved in SequenceME but I do know that AfME have put a lot of work into getting things to this stage. As you say this project is likely to need institutional/government funding but without the work of AfME, who like all charities rely on donations to fund their work, it is unlikely that this project would exist to need such funding.
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What sort of work does AfME do in this context?
 
Andy said:
As an additional note, I've had it fed back to me that those working on funding possibilities for this project have found the suggestions made in this thread to be useful, so thank you all for those.
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Another idea is Vitalik Buterin.. he has funded a lot of long Covid projects. Don’t know if he’d do anything for ME. His foundation — Balvi — says it’s no longer accepting applications though.
 
Andy said:
For those who might be considering, or might consider, a donation to AfME in support of this project, I saw on one of their social media they give this reply to another member of the community,
"It is possible to restrict your donation to support our research work, including the setup of the work packages and fundraising for studies. This can be done by letting us know, when making a donation, that it is for research.”
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I contacted AfME to ask if fundraisers on platforms such as Justgiving and Facebook can be restricted to supporting their research work. Ruth Richardson, Director of Fundraising and Development replied:

"We can certainly restrict to Research any income raised via fundraising platforms such as Justgiving or Facebook. In order to ensure the restriction is applied we just need to be made aware of this via an email to fundraising@actionforme.org.uk
If a link to the fundraising page can be included in the email that would be very helpful too."​
 
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Chris Ponting said:
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.”
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The abstract says (broken up for readability):

Standard genome-wide association studies (GWAS) and rare variant burden tests are essential tools for identifying trait-relevant genes. Although these methods are conceptually similar, we show by analyzing association studies of 209 quantitative traits in the UK Biobank that they systematically prioritize different genes.

This raises the question of how genes should ideally be prioritized. We propose two prioritization criteria: 1) trait importance — how much a gene quantitatively affects a trait; and 2) trait specificity — a gene’s importance for the trait under study relative to its importance across all traits.

We find that GWAS prioritize genes near trait-specific variants, while burden tests prioritize trait-specific genes. Because non-coding variants can be context specific, GWAS can prioritize highly pleiotropic genes, while burden tests generally cannot. Both study designs are also affected by distinct trait-irrelevant factors, complicating their interpretation.

Our results illustrate that burden tests and GWAS reveal different aspects of trait biology and suggest ways to improve their interpretation and usage.​

Any chance anyone can do a 'for dummies' summary of that? I'm surprised that a GWAS isn't just a sketchier version of a WGS study.
 
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Andy said:
...the commonly quoted time for sequencing the whole genome of one sample is about 24 hours. I don't know how many samples Nanopore can sequence at once, and whether their technology is any faster than existing methods, so it is a bit difficult to guess how long they might take to process 10,000, or the planned 17,000 - analysis of all that data, and it is a lot, will also take a significant amount of time.
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I think this 2023 preprint maybe tells you but I don't understand it.

But look at that DNA go, in this video! As a 'naked' half of the strand goes through the nanopore, which has an electrical charge, each DNA letter (A, T, C or G) gives a different electrical signal of disruption of the field that can be read in sequence (I think).

 
Sasha said:
I think this 2023 preprint maybe tells you but I don't understand it.
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Says this:
Together, the DNA processing and library preparation take approximately 20 hours over two days to process up to 16 samples in a single batch, and the PromethION whole genome sequencing takes 72 hours (Figure 1).
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With the largest machine, you can run ~5,000 sequences a year. I assume the prep can be done while you run another batch, so it doesn’t add time to the processing duration. I have no idea which machines they use and how many.
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Source
 
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Andy said:
As an additional note, I've had it fed back to me that those working on funding possibilities for this project have found the suggestions made in this thread to be useful, so thank you all for those.
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The Advanced Grant from EU is 2.5M, with an additional 1M in setup costs. Could be put together with other funding. https://erc.europa.eu/apply-grant/advanced-grant

Also, have found that Vinod Khosla reads emails and has someone respond, so do hope team request funding from him.
 
Is it mentioned anywhere what resolution the WGS will be?

Would it make sense to increase the resolution on HLA genes to 100 given the Zhang study findings and the fact HLA is notoriously error prone in sequencing.
(Since it’s a relatively tiny part of the genome it wouldn’t cost that much to increase resolution a lot here in the grand scheme of things).
 
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