Webinar Recording and Transcript – March 2024

DecodeME the ME/CFS study · March 2024 DecodeME Webinar

Read the transcript:

SONYA

Hello and welcome everybody to another DecodeME webinar. I’m joined today by colleagues Chris Ponting and Andy Devereux-Cooke and they’ll be speaking in a moment want to welcome those people who are watching on the webinar, and those who have joined us through Facebook.

Today we want to talk to you about our plans and next steps, and we will have an opportunity for questions. We are going to talk to you about the DecodeME study extension. We know that this may be a disappointment and frustration, we feel the same, so we want to share with you a little bit more information about that. Firstly, I can honestly say, hand on heart, the whole team has been working incredibly hard in the background; that includes our PPI, patient public involvement members, people with lived experience, the team in Edinburgh, the team at Action for M.E., and others that we’re working with.

So, as many of you will know, we were originally due to complete the DecodeME study by August, this year. Throughout the project, and we’ve talked to you previously about some of them, we have faced challenges which have affected the timeline. Things like Amazon buying up all the boxes during the pandemic and lockdown impacted on us. We’ve had postal strikes and we’ve had changes in the people that have been working with us in we call the ‘supply chain’.

However, we’ve managed to overcome these.  But, the one challenge that we were not able to overcome was the operational and capacity issues at UK Biocentre, and they’ve been the most significant factor affecting our project completion timeline.

While we have been able to mitigate some of the delays and worked incredibly hard with UK Biocentre, with meetings every week, sometimes every single day, to try and overcome the issues, we have not yet got all the data that we expected to have back from them at this point. When participants sent their samples in, they went to UK Biocentre, to be processed after which the data is send back to Edinburgh University.  However, we have not yet got all of that data back.

I want to reassure you that nothing is going to happen with the samples that have been sent in. We will get the data. It’s just taking longer than we had expected.

And as a result, we now need more time in order to quality check and analyse the genetic data.

The people that have taken part in the study, completed questionnaires and sent in samples, have done an amazing job, but the next step, the extraction of that DNA from the saliva samples, at UK Biocentre, is what has really caused delays.

In short, we didn’t have enough time to perform all of the analysis required by August 2024, so we approached are funders and they have agreed to give us an extension.  They have funded us for another year to enable us to do the work that we need to.

We discussed this situation with our Scientific Advisory Board, as well as our funders, and they also agreed with our assessment that the extension should give us sufficient time to finish the project.

I can honestly say, and you’ll hear this from Chris and also from Andy, people are working really hard and are committed to completing this research to the highest possible scientific standards, ensuring that our findings are as robust as possible.

We all know in the community that there have been many false starts and we are dedicated and committed to making sure that our findings are scientifically valid.

Our funders have given us extra money so that we keep the team in place, and it’s quite a large team, and they’re having to work really hard with quite a lot to do, but we will ensure that we deliver as soon as we can and give results as soon as we can, but we will only do that when they reach the standard required.

We are now working to a deadline of August 2025 and as I said we will release the results as soon as possible before this date.

I’m now going to hand over to Chris, who is going to tell you a little bit more about the work that we’re actually doing at the moment.

CHRIS

Thank you Sonya.

Participants who provided DNA will remember that you sent your samples to UK Biocentre, and that is, for us, the beginning. There are so many steps after that but for you, you probably don’t know so much about what happens afterwards. So, I just thought I would go through each of the steps in turn to help you understand the complexity of the operation and what has caused the delays.

Firstly, when the samples arrive at UK Biocentre, the sample is split into two, and the second sample is kept for future research. The important thing is to say that each sample is incredibly valuable to us and we’ve managed to communicate to UK Biocentre, how valuable each sample is by going to visit them with members of the PPI team.

When UK Biocentre takes receipts of each sample, it associates a barcode with the sample, which allows the tracking of the sample going right from that point until the end when we do the analysis.

The amount of DNA in each sample then needs to be measured and after that the extraction occurs, and there is the ‘replating’ – this is means taking a portion of that sample and putting it onto a plate that, with other samples, which then goes to ThermoFisher, for genotyping. This is the second step.

Our plans have been very extensive. We have been planning for many years, but we didn’t plan for this. So, what’s been going wrong is that, at times, the samples have not been receipted properly when they turned up at the door of UK Biocentre. At times the tracking, with the barcode, wasn’t done to the highest standards and not all of the quantification of the DNA was done perfectly. So, there have unfortunately been errors and inconsistencies in the process that have caused us to meet with UK Biocentre twice a week to go through, literally sample by sample, what has happened for each one of them.

UK Biocentre have engaged in that process very well indeed. We have to thank them for that. They have produced a 62-page report about all of the different samples and what are the issues. We have gone through all of the checks, that they have now employed, and we’re signing that off soon. The first version of that report goes back to last summer. So, you can tell that we’ve been…. Well, I hope you can tell, we’ve been working hard on that every week, for those two meetings and holding to account the organisation that has been doing the work. This has not been something that we have been able mitigate.

The funders, when they gave us the extra money, said that their panel agreed that the major delays had been outside of the control of the principal investigator, ourselves, and were being actively managed by ourselves.

So, the first set of plates with the DNA samples have gone to ThermoFisher and have come back. The data coming back to us is the third step in the process, where we compare the data with UK Biobank controls and we’ve done that now for the first batch.

Last week we got back the second set of data, the second batch, and we’re looking through that now, making sure that it’s of high-quality and it does look like it’s of high quality.

There’ll be two more of those batches, which will come really quickly, because I’m pleased to tell you that there is no backlog of DNA extractions. Extractions are almost complete, but of course we’re still meeting twice a week to ensure that happens.

So, by the summer, we’ll have all of the data and will do the data cleaning, what’s called ‘quality control’, and then we’ll be comparing it with the DNA that comes from UK Biobank, which represents healthy controls.

This comparison should allow us to say where in the genome there are letter changes that are more frequent among people with ME than those in the general population. This indicates where in the genome there are risk factors for ME, which hopefully will tell us what are the systems that are going wrong in people with ME. If it’s the nervous system, the immune system, mitochondria, autonomic system etc.

That will allow us to put together all of the results and we will write them up as soon as we can for peer review, knowing that we have done the best possible job and we’ve done all the checks and balances.

Whatever we find, we have to make sure it’s robust.We’ll do everything we can in-house but there is an additional way that we can ensure that what we’ve found is correct and right and true, and that is to collaborate with others on a replication of the finding.So, ahead of time, and we’re announcing today, that we are collaborating with Hanna Ollila and Anniina Tervi from FinnGen, in Finland, who already are analysing ME data from electronic health records from different sources. From Finland, we are collaborating with FinnGen, and from the USA, we are looking to collaborate with the Mass General Bridgham Biobank, and also the Estonian Biobank. This then becomes an international effort using thousands of people’s data, with DecodeME, to ensure that we together, internationally, have the best results for the community as possible.

It isn’t an academic exercise. What we are doing is to try and accelerate research towards clinical trials and new drug targets as fast as we can.

So, we are up in the top left. We are doing the genetics and we are trying to find these hits, which are the red circles, that will lead us to understanding what’s going wrong for people with ME and how the different genes and variants relate to one another in a disease network. That will help to, potentially, repurpose drugs if there are any. We’ll compare it to known drugs and databases and from that there will be an opportunity to test drugs in trials on cases and controls.

Now, of course, we’re only in the top left-hand corner of this graph at the moment, but we’re planning ahead. As many people know, we are already working with PrecisionLife, an artificial intelligence company, who have partners in Pharma, so that will then provide an acceleration of anything that we produce from DecodeME into the right fields towards new drugs and new drug targets.

ANDY

Thank you Chris and Sonya.

I’m here to finish up our slides. As you can see, we’ve got a project update on the numbers of people who have taken part.

We started with almost 38,000 people who signed up to the study, who created an account with us.  Just under 27,000 of you completed the first questionnaire and just that part alone provided a lot of valuable data which will be of use moving forward.

From those, just under 22,000 were invited to provide DNA. Just over 18,000 of you have returned those DNA kits and just over 15,000 completed the second questionnaire.

All of that is a fantastic result. As a patient myself, I can be tempted to look at those figures, particularly the top line and think we started with a large number, but then we’re losing them, losing numbers as we go down.

That is something that happens in studies. For various reasons people do not take part in the next stage, which obviously is their choice, and even to get to the second questionnaire, where over half of you were willing to take part in that, just shows what a fabulous contribution you’ve all made to DecodeME, thank you. Thank you all for your efforts. I know personally, the cost in energy and time that takes.

In terms of next steps, well we’ve already kind of covered it. We are going to continue to send those batches of DNA to ThermoFisher for genotyping, get that genetic data back, and do all the necessary analysis, which is more easily said than done.  It takes far more time to actually do that analysis than, obviously, to say that sentence!

We will publish the results eventually. That will come, well, ultimately, when it’s ready. There is great awareness throughout the team that we would like to do this as quickly as possible, but that is balanced against the quality of our final output and ultimately within the time limits that we have. We are aiming for high quality of that final output, because that will provide a starting point and a continuation for further research in the future.

As you can see on the next slide, we are going to be opening up our access process for the data. This process will allow other researchers to apply to us for access to that data to inform and form the basis for future research from them. We’re also going to continue working on plans to build longevity, as much as we can, for the DecodeME cohort. Basically, looking forward again to provide value to the community for not only for the money given to us by the funders, but again, the energy and time that you have invested in us.

 

SONYA

Thank you Chris and thank you Andy.

We’ve had lots of questions coming in. The first question that I wanted to pick up is related to what you were saying, Chris, about some of the delays. And I think it would be really helpful if you could just talk a little bit more about the DNA samples.

People are concerned that they might have been lost due to the issues at UK Biocentre and are worried that if there have been issues with those, that people are going to be asked to provide another DNA sample.

So, could you possibly just say a bit more about the situation?

CHRIS

Thank you Sonya.

So, where samples were lost, and there were a couple of hundred that were lost, we’ve gone back and asked people for a second sample. We were already asking some people for second samples because sometimes the sample that’s provided doesn’t process, for a whole variety of reasons, and when that happened and there wasn’t enough DNA, for example, then we asked people for a second sample.

So, all of that was happening behind the scenes. I don’t have the numbers in front of me, but that was happening all the way through and we made sure that people could be given the opportunity of giving a second sample, because our value is that every single sample is incredibly important. We took that as a value right from the beginning and then we followed it all the way through.

There were cases downstream of that, the sample is not able to be taken forward, all the way down the process to the analysis. For example, where the DNA letter changes are read out, some of those are not taken forward. Those are minor. 99.8% of people, 99% of people, I don’t know what the number is. You can be reassured that your sample has been treated incredibly well, from receipt to data analysis, and that we’ve done all that we can to ensure that the value that it has is translated into scientific value.