Gene expression meta analysis study, and a blind trial, proposed by Professor Kellam

[Bob]

Gene expression meta analysis study, and a blind trial, proposed by Professor Kellam

There's not much information on this yet...

It's sort of a continuation of Dr Kerr's work...



CFS Research Foundation

The Foundation has awarded a grant to Professor Paul Kellam, Virus
Genomics Team Leader at the Wellcome Trust Sanger Institute, Cambridge
and Professor of Viral Pathogenesis, Department of Infection, University
College London, along with Dr Tim Harrison, Reader in Molecular Virology,
Department of Internal Medicine, University College London Medical School
and Dr Daniel Frampton, Research Fellow, Department of Infection,
University College London for a study:-

"Meta analysis of gene expression data to discover diagnostic and mechanistic
signatures in the peripheral blood of CFS patients".

In recent years other groups of researchers have published on the involvement
of genetic factors in CFS/ME. Using advanced computing the results of these
studies will be analysed together with those derived from Dr Kerr's work.

http://www.cfs-research.org/research-current.htm

 

[Esther12]

This stuff has never sounded that promising to me, but it will be interesting to see how/if it works out. At this point, I wouldn't expect a blinded trial to be able to distinguish between CFS and controls with much confidence. I might be totally wrong though.

 

[Bob]

This stuff has never sounded that promising to me, but it will be interesting to see how/if it works out. At this point, I wouldn't expect a blinded trial to be able to distinguish between CFS and controls with much confidence. I might be totally wrong though.

The CFS Research Foundation's website says they have funded a lot of Dr Kerr's research. Their website lists a blinded study that Dr Kerr carried out, using his gene expression findings, and apparently that study failed. I don't think I've ever heard about that failed study before now, as I would have been very interested in the results, and I don't remember hearing about it.

Sep 08 - Jul 10
Blinded class prediction (Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) versus Normal) using gene expression data and an artificial neural network (ANN)
Grant = 135,514
Dr J Kerr, St. Georges University of London
http://www.cfs-research.org/projects.htm

 

[eric_s]

Wellcome Trust Sanger Institute, University College London... i don't have the best memories associated with these names.

That does of course not mean these researchers here don't have good intentions, but nevertheless, it caught my eye...

Also interesting that most are specialists for viruses or infections.

I would like to know more about this CFS Research Foundation. I always thoght it's Dr. Kerr's foundation, but obviously it's not. Kellam is actually part of the Scientific committe and there's also a UCL guy on there. So they are giving the money to themselves. That does not have to be bad, i'm only saying what i can read there.

It would be interesting hear Dr. Kerr's opinion.

 

[Esther12]

@ bob:

I don't really understand the science behind this gene expression work, but to me, Kerr's stuff looked like post-hoc pattern finding from fairly random results. It actually reminded me of a lot of psychological CFS stuff in that regard. There could well be something to it, but it didn't look as compelling as I thought it was from the positive press that greeted his initial work.

(I feel a bit bad criticising Kerr's work, as I always felt like he was a decent guy trying to help us, and it felt like his work with CFS has ended badly for him. So still plenty of love to Kerr!!)

 

[Bob]

@ bob:

I don't really understand the science behind this gene expression work, but to me, Kerr's stuff looked like post-hoc pattern finding from fairly random results. It actually reminded me of a lot of psychological CFS stuff in that regard. There could well be something to it, but it didn't look as compelling as I thought it was from the positive press that greeted his initial work.

(I feel a bit bad criticising Kerr's work, as I always felt like he was a decent guy trying to help us, and it felt like his work with CFS has ended badly for him. So still plenty of love to Kerr!!)

Yep, I think I agree with all of that Esther.

I used to be more hopeful about gene expression studies, but they just haven't come up with any conclusive biomarker results, as far as I know, and they've been doing the studies for a long time now.

 

[Bob]

Wellcome Trust Sanger Institute, University College London... i don't have the best memories associated with these names.

That does of course not mean these researchers here don't have good intentions, but nevertheless, it caught my eye...

Also interesting that most are specialists for viruses or infections.

I would like to know more about this CFS Research Foundation. I always thoght it's Dr. Kerr's foundation, but obviously it's not. Kellam is actually part of the Scientific committe and there's also a UCL guy on there. So they are giving the money to themselves. That does not have to be bad, i'm only saying what i can read there.

It would be interesting hear Dr. Kerr's opinion.

hmm... all of that looks slightly concerning.

 

[oceanblue]

@ bob:

I don't really understand the science behind this gene expression work, but to me, Kerr's stuff looked like post-hoc pattern finding from fairly random results. It actually reminded me of a lot of psychological CFS stuff in that regard. There could well be something to it, but it didn't look as compelling as I thought it was from the positive press that greeted his initial work.

Afraid I agree with you. When Kerr's initial gene expression came out I got terribly excited as he seemed to have found the holy Grail of CFS and it's subgroups. When I phoned up the CFS Foundation for more info and was told he'd discovered 7 subgroups in a sample of 21 patients I was speechless. Honestly, we need researchers with good intentions but we need more than good intentions to get to the bottom of this illness.

Sometimes I think we are too soft on biological research simply because it's not psychological research. I'm desparate for progress in understanding this illness but so often I read bio research papers and despair at the lack of quality. I'd struggle to name more than a few really good CFS research papers (would have put the Lombardi Science XMRV paper top of the list but...)

Interesting about the blinded research proving negative. I wonder if they tried to publish or if no one wanted it; seems like a perfect example of how publication bias comes about.

 

[Esther12]

Sometimes I think we are too soft on biological research simply because it's not psychological research. I'm desparate for progress in understanding this illness but so often I read bio research papers and despair at the lack of quality.

Possibly. I think that poor biological research is much less likely to be actively damaging than poor psychological research. It's sad that my standards are so low that I'm relatively pleased with medical research which doesn't make things worse for us.

Also - CFS is difficult to do good research for. I've got no idea how we should make progress with it. It's currently just defined by a symptom - and one that is commonly caused by just about every health problem going. Then people are surprised when no consistent abnormalities are found in patients!

CFS is such a joke. Worst diagnosis ever.

 

[eric_s]

Possibly. I think that poor biological research is much less likely to be actively damaging than poor psychological research. It's sad that my standards are so low that I'm relatively pleased with medical research which doesn't make things worse for us.

Yes, but then why don't change your standards? I think that's very necessary, for all of us. We have accepted discrimination and a treatment that is really beyond bad. We should demand what everybody else is getting and not be happy before we get that. We are not some sort of second class citizens, not at all... As soon as we are all aware of how wrong the situation is, we might be able to get more people to act and then we can move things.

Also - CFS is difficult to do good research for. I've got no idea how we should make progress with it. It's currently just defined by a symptom - and one that is commonly caused by just about every health problem going. Then people are surprised when no consistent abnormalities are found in patients!

CFS is such a joke. Worst diagnosis ever.

It might be that CFS is more difficult than other illnesses, but i'm pretty sure if there was similar funding as for other groups, there would be progress. Science has been able to solve so many problems, why should this be different. And not even "CFS" is only defined by one symptom, at least not according to the Fukuda definition. Maybe there is a definition that does not require any other symptom than fatigue, but there's no reason to use that one then. At least not if you want to find something.

 

[Esther12]

I'm probably just being a bit moody eric. I need a holiday, and I'm not going to get it.

 

[eric_s]

Sorry, i didn't want to bother you. I just think it's important we try to see things from outside of our abnormal perspective, from the perspective of anyone else.

 

[Esther12]

Sorry, i didn't want to bother you. I just think it's important we try to see things from outside of our abnormal perspective, from the perspective of anyone else.

Good to be put right! - you bother away whenever you see the need. I quite agree that it's good to try to see different view-points.

 

[Snow Leopard]

I think they should do it as a post- exercise study (eg exercise two days in a row, test gene expression after second session) and compare to fitness/activity matched sedentary controls.

Probably not going to happen though.

 

[Dolphin]

Second part of the Prof. Kellam research will be a blinded study

The second part of the Prof. Kellam research will be a blinded study based on the results of the meta-analysis - it's in their newsletter.

 

[Dolphin]

Also interesting that most are specialists for viruses or infections.

It used to be called the Persistent Virus Disease Research Foundation. That's the sort of area (virology, infection, etc.) the scientific committee has generally come from.

I would like to know more about this CFS Research Foundation. I always thoght it's Dr. Kerr's foundation, but obviously it's not. Kellam is actually part of the Scientific committe and there's also a UCL guy on there. So they are giving the money to themselves. That does not have to be bad, i'm only saying what i can read there.

It would be interesting hear Dr. Kerr's opinion.

As far as I know, Dr. Kerr has left the field. I can understand why you might think it was Dr. Kerr's foundation as for a few years, his research indeed was all that they were funding.

One can see the research they have funded at: http://cfs-research.org/projects.htm .

 

[Dolphin]

I think they should do it as a post- exercise study (eg exercise two days in a row, test gene expression after second session) and compare to fitness/activity matched sedentary controls.

Probably not going to happen though.

That would be good.

However, a meta-analysis of the existing studies also has a value. I always had my doubts about Dr. Kerr's subsets until they were tested (sometimes one sees studies where the researchers then test their theories on another group within the same paper to see if they have validity or not).

Unfortunately, I think the meta-anlysis means they are likely to include the CDC data (from patients chosen using the so-called "empiric" criteria) so I hope to write to them about this. However, I really have another job I need to finish and stop procrastinating over before doing that (writing to them). If other people want to write to Prof. Kellam [to tell him to not include the CDC data, or also analysis the data without it] that would be good. It wouldn't matter if they got more than one person writing and time may be of the essence so people writing quickly would be good.

 

[Snow Leopard]

Wait, where is the discussion of a blind trial? Is this going to be based on what was predicted by the meta analysis, or have I filled in too many blanks?

 

[oceanblue]

CFS is difficult to do good research for. I've got no idea how we should make progress with it. It's currently just defined by a symptom - and one that is commonly caused by just about every health problem going. Then people are surprised when no consistent abnormalities are found in patients!

Agreed, the central problem is that CFS is such a hard problem to tackle (and the case definition is probably the place to start). But it's because CFS is so hard to tackle that we need really excellent research to get anywhere: no amount of mediocre research will get us anywhere, as I've noticed over the 17 years I've been ill. I'm hoping that Stephen Holgate's MRC initiative on biomedical will help kick start things, though I wouldn't put any money on it.

I think Snow Leopard is right about exercise challenge being part of the solution.

Back on topic, I like the sound of the Kellam research, a meta-analysis of what's been done to date on gene expression followed by a blinded study based on the meta-analysis findings.

Dolphin: Really good point about not including CDC-empiric defined patients - could you let me know the relevant CDC paper(s) and I'll try to write?

 

[eric_s]

It used to be called the Persistent Virus Disease Research Foundation. That's the sort of area (virology, infection, etc.) the scientific committee has generally come from.

As far as I know, Dr. Kerr has left the field. I can understand why you might think it was Dr. Kerr's foundation as for a few years, his research indeed was all that they were funding.

One can see the research they have funded at: http://cfs-research.org/projects.htm .

Thanks, Dolphin. I think it's good the investigators come from the corner of viruses, infections, etc. The reason why i wrote my comment was that the Wellcome Trust Sanger Institute and UCL were the ones that presented their negative studies around December of last year and then put out a press release saying XMRV does not play a role in ME/CFS and is only contamination. But they also said that it's not XMRV, but might be another virus. So i found it a bit interesting that this group now sends their virus people to investigate ME/CFS, but it doesn't have to mean anyhting. I just don't really like the Wellcome Trust and UCL anymore after this story. Even if in the end they would turn out to have been right about contamination i think this was premature at the time and i didn't like the way it was pushed to the news media.

Regarding such a study with an exercise challenge, isn't this what the Light study has done? I think they didn't put the participants through exercise on two consecutive days, but they studied changes in gene expression after exercise. Maybe a more limited number of genes than in the studies they will be looking at here, i don't know.