#OMFScienceWednesday-Severely ill Big Data Study

[Ben H]

Hi guys,

On this #OMFScienceWednesday, we review the Severely ill Big Data Study.

This study, led by Drs. Davis and Xiao, included over 1,000 tests per patient, producing, to our knowledge, the biggest dataset ever generated in a cohort of ME/CFS patients. This big data study examined the patients’ genome, gene expression, metabolomics, microbiome, cell-free DNA sequencing and quantitation, and cytokines, as well as a range of tests typically performed by clinicians.

In 2017, the focus of the study was on analysis, data integration, and making the dataset available to researchers at The Stanford End ME/CFS Data Center(registration required).

· Differences in metabolites, microbiomes, cytokines, and several clinical test results were observed between patients and controls.

· No significant differences were found for any major DNA viruses between patients and controls using cell-free DNA from the blood. By using cell-free DNA it was possible to look for even the viruses that can hide behind the blood-brain barrier escaping detection by normal means. In addition, the blood of patients was examined for new pathogens by isolating particles from the blood and using DNA sequencing. No new pathogens were found.

· SF-36 scores are worse in ME/CFS than in several other major diseases and correlate the least with depression and mental illnesses. (SF-36 is a questionnaire in which patients report on their fatigue and other aspects of their quality of life.)

· Genetics have been a particularly interesting aspect of this study, as the team has identified several candidate genes that may predispose individuals to develop ME/CFS (or severe ME/CFS). This is exciting because it may tell us about the root cause of the disease – which still remains a mystery.

· Amping up the analysis is a priority given the complexity of this dataset. OMF has funded a full-time bioinformatician at the Stanford Genome Technology Center to help complete the analysis of this dataset and publish it in the scientific literature, and to continue integrating it with future projects.


B

 

[Hopeful1976]

I'm so grateful to the OMF but I can't help but feel gutted each time I read that 'data still needs to be analysed'. I really feel that the elusive driving force behind m.e will never be found. Surely by now, Ron and the team would have found the cause

 

[caledonia]

· Genetics have been a particularly interesting aspect of this study, as the team has identified several candidate genes that may predispose individuals to develop ME/CFS (or severe ME/CFS). This is exciting because it may tell us about the root cause of the disease – which still remains a mystery.
B

Good to hear!

 

[caledonia]

I'm so grateful to the OMF but I can't help but feel gutted each time I read that 'data still needs to be analysed'. I really feel that the elusive driving force behind m.e will never be found. Surely by now, Ron and the team would have found the cause

It's going to happen, don't worry. The Human Genome Project was finished two years earlier than projected, as they developed more rapid methods of analysis as they went along. Ron is working on speeding things up for us too.

 

[AdamS]

Thanks for the update Ben as always. Good news re the bioinformatician too.

 

[Diwi9]

Looking forward to publication!

 

[Murph]

My favourite part of this is that they're sharing:

making the dataset available to researchers at The Stanford End ME/CFS Data Center(registration required).

That is just terrific. I totally support OMF's approach of defying the broken academic incentive structures that make people zealously horde data and release it only via publication in journals. Collaboration = acceleration.

A more middling part is this:

Differences in metabolites, microbiomes, cytokines, and several clinical test results were observed between patients and controls.

It looks like they've confirmed the kind of issues we already knew about rather than finding any new great thing? That is good, I guess.

The part I am concerned about is this:

as the team has identified several candidate genes that may predispose individuals to develop ME/CFS

Perhaps I'm ignorant of potential treatments but I can't help feeling that if it's largely genetic, a cure will be rather difficult. CRISPR surely can't be our white knight. Can it?

 

[Runner5]

Has any study looked at the modern food supply and CFS / ME?

 

[caledonia]

The part I am concerned about is this:
Perhaps I'm ignorant of potential treatments but I can't help feeling that if it's largely genetic, a cure will be rather difficult. CRISPR surely can't be our white knight. Can it?

Most genes are potentials which get expressed in the presence of various environmental stressors. Very few diseases are caused by a gene which is a slam dunk that you will get a disease.

At any rate, knowing what the causative genes are opens up possibilities for treatments, and perhaps prevention for others with the same genes.

 

[wastwater]

The last gene they mentioned NRXN1 is thought involved in autism and schizophrenia there maybe lots of sites like this in the genome and they could be immune related still as I’m not sure autism and schizophrenia have been figured out yet
I’m interested in the area around 6p25 and on paper it seems to be a similar risk site

 

[Hopeful1976]

It's going to happen, don't worry. The Human Genome Project was finished two years earlier than projected, as they developed more rapid methods of analysis as they went along. Ron is working on speeding things up for us too.

I hope so. I really really hope so. The worst part of this is losing hope. I imagine the day it's figured out. I dream of it becoming reality.

 

[TreePerson]

Hi @Ben H

Do you know if Dr Davis still has plans in progression to develop a more reliable way of testing for the RNA viruses? I think I’m right in saying these include enteroviruses and are ones that he so far hasn’t been able to test for?

As these have historically been linked to ME/CFS it would seem an awful shame to say we have excluded all viruses except these ones. It would leave a huge question mark hanging.

 

[JES]

Enteroviruses are difficult to detect from blood, especially the chronic non-cytolytic form that Dr. Chia suspects is linked with CFS/ME. Dr. Chia has detected enteroviruses in roughly 80% of his patients versus 20% in controls. This still does not prove that enteroviruses are the causative agents in CFS/ME, but it puzzles me how Chia managed to get this result while others don't seem to find any difference in viruses between patients and controls. Obviously both of these results cannot be correct.

This would be something to ask Davis about in a Q&A, because obviously he is aware of the research and results of Chia. All it would take is one well conducted study on a large patient group (like these 1000 patients for example) to possibly disprove the hypothesis of enteroviruses, so this research would be extremely valuable, even if the result would come out as negative.

 

[Neunistiva]

Perhaps I'm ignorant of potential treatments but I can't help feeling that if it's largely genetic, a cure will be rather difficult.

I am speaking as a complete laywoman here, not really knowing what I'm saying, but I remember Dr. Naviaux saying if Suramin works to pull us out of CDR, we may have to take it ocassionally again if we fall back into CDR, as we might just be predisposed to falling into it.

I imagine whatever Dr. David is working on right now to pull us out of metabolic trap may be like that as well. I'd lived my life for 23 years without falling into ME/CFS state. So maybe they pull me out of it, but because of my genetic predisposition some virus or other trigger throws me right back into it a decade or so down the road. Then I take the treatment again.

As I said, I'm totally speculating here without much real understanding.

The post does say that genetic factors may uncover the root cause so that's something to look forward to as well.