Webinar 2pm today (Friday 6 June 2025): Genetics Centre of Excellence (Edinburgh Ponting lab): update on recent research

Sasha

Sasha

Senior Member (Voting Rights)
This sounds great! Action for ME are putting on a webinar with the latest research updates from Prof. Chris Ponting's Edinburgh lab, with presentations from Dr Audrey Ryback and PrecisionLife, plus a Q&A with PPI (patient and public involvement) representatives (I assume from DecodeME?).

You have to register but if you can't attend, there'll be a recording.

You can submit a question in advance. (Quick! Quick!)

Here's the link.
 
Audrey is now looking at proteomics and the Beentjes paper. So more exciting stuff from her and a really clear presentation I thought.

PrecisionLife. An odd definition of PEM and saying they can see it in mice… (maybe I misunderstood)
Beyond that it seems to be repeating what we’ve already seen in their previous papers. Talk of subgroups, inflammation, energy metabolism, etc. I didn’t find their presentation as interesting although I am very interested in their approach. I think there just wasn’t much new here and more commercial sensitivities, so still waiting for results/reproduction and then what drugs they are looking to trial (in the US).
 
Yes, Audrey was very clear. She had presented this negative story for us at UCL in a preliminary form but I gather this is now due for publication.

The Precisin Life presentation was interesting but I have to say that it is much more difficult to follow their methodology and analytic procedures than it has been for the Edinburgh group whose account is always transparent a a level almost anyone can follow.

The continuing puzzle is how Precision Life appear to have made massive progress with everything when high quality scientists we know well are still struggling to replicate findings or to come up with just one or two few findings they have confidence in.

It looks as if PL have found some susceptibility genes but their method of dividing patients up into groups to me makes things more difficult to follow, rather than easier. I am thinking that maybe what they have found are some genes that affect susceptibility simply because they are needed for optimal function of target organs. I get no insight into the underlying mechanism from any of their hits. In contrast, genes like MHC seem much more likely to tell us about what starts the whole thing off.

The discussion of repurposing drugs seemed to me pretty unrealistic, without a whisper of a model for upstream mechanism. Why is Oystein Fluge struggling valiantly with complicated biologics if you just need some old pill we already have?
 
hotblack said:
PrecisionLife. An odd definition of PEM
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I thought it was odd too. IIRC, they said they had a subgroup that had PEM, and they said that PEM was fatigue after exertion (no!). I was also confused about how only one subgroup had PEM if all their sample had ME/CFS - they should all have had PEM. I wonder if the person presenting mis-spoke or if my memory of this is wrong. I was confused about whether there was a paper where we could look this up (not PL's fault, I think I may just be a bit brainfoggy today).
 
Sasha said:
I thought it was odd too. IIRC, they said they had a subgroup that had PEM, and they said that PEM was fatigue after exertion (no!). I was also confused about how only one subgroup had PEM if all their sample had ME/CFS - they should all have had PEM. I wonder if the person presenting mis-spoke or if my memory of this is wrong. I was confused about whether there was a paper where we could look this up (not PL's fault, I think I may just be a bit brainfoggy today).
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The original segmentation and SNP list was in this paper. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03815-8#Tab1

Maybe I misunderstood but I got the impression that it was not meant as mutually exclusive (ie one 1 phenotype having pem) but more just a more predominant feature in that group in analysis they did?

You would expect the replication study to be interesting as DecodeME will have people with severe illness whereas the UK Biobank won't due to its requirements for attendance for tests. It makes me wonder if that may actually reveal a few extra phenotypes or just show certain of those they have found are particularly susceptible to severe illness.

I submitted a question about studying severe illness phenotypes but it didn't get answered.
 
I had the familiar experience of feeling a huge amount of hope when they talked about drug trials and my enthusiuam being somewhat dampened by coming on here and reading this thread :dead:. (of course this is part of what makes s4me so valuble!)

Did anyone catch that they are planning to do trials in Australia with Chris Armstrong's team?

I am especially interested in the 'protective biology' concept. I really hope that there is something to this drug repurposing stuff but yes it all seems a bit too good to be true.

I do feel like for proprietary reasons they are not as clear as I would like them to be. They seem to have the trust of A4ME and the Edinburgh team, which makes me trust them more than I otherwise would. But important to keep in mind they are a buisiness.
 
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I think if Precision Life want to be taken seriously by the patient community they need to present their science in a way that the community can judge its quality. I go the impression they were talking as 'we, the scientists, have found these really great results, and that isn't have of it, there are even more great results here...' without doing what scientists are supposed to do - which is explain how they reach the conclusions they do from the evidence.

I find it hard to see how you can divide patients up into twenty-odd groups, each conveniently with a gene telling you what caused their brand of disease. Especially when previous experience indicates that with this number of subjects you are unlikely to find anything reliable in the genetics. I thought the combinatorial method sounded interesting but they told us nothing about that.

I don't know the details of genetics methods but I do know that every time Chris P presents I know exactly what his data mean and why.

Am I being too critical?
 
Kiristar said:
Maybe I misunderstood but I got the impression that it was not meant as mutually exclusive (ie one 1 phenotype having pem) but more just a more predominant feature in that group in analysis they did?
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That’s my understanding too, it’s not saying we’re completely different diseases more that people have more of a predisposition towards certain symptoms. And since they’re focused on symptomatic relief through drugs which work on certain pathways it makes sense to look at it that way. That’s their business as far as I can tell.

But that comes from my understanding of the company and previous papers, I’m with @Sasha on it not really being clear in their presentation.

V.R.T. said:
I do feel like for proprietary reasons they are not as clear as I would like them to be. They seem to have the trust of A4ME and the Edinburgh team, which makes me trust them more than I otherwise would. But important to keep in mind they are a buisiness.
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You could well be right. It had more of a business presentation feel to me. Maybe they just weren’t able to present the data they wanted yet? It’s great to have a team like that and their technology involved. And please don’t dampen your enthusiasm too much. I thiught it was a great session overall :) Audrey was just the highlight for me despite it being a ‘negative’ result. I’m very positive and hopeful abiut where this is all heading.
 
Jonathan Edwards said:
Am I being too critical?
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Given that they are using their own 'black box' analysis of genetic data, I think it's reasonable to ask them to demostrate that it provides accurate results when applied to other conditions where more is known about the genetic predispositions, subgroups and treatments that work.

So they should be given, by an unconnected group of scientists, a set of genetic data for a condition and not be told what it is, and asked to analyse it the same way, and another set of randomly selected genetic data and not told which set relates to a specific condition. In other words, has the black box been tested?

Maybe they have proved themselves in that way already for other conditions. I haven't kept up with their literature.
 
Jonathan Edwards said:
I think if Precision Life want to be taken seriously by the patient community they need to present their science in a way that the community can judge its quality.
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I want to understand what's going on in the black box but equally, I don't understand what's going on in the Zhang black box! I understand how a basic GWAS works but not these other computational approaches and so I have no idea to what extent the results can be trusted.
 
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