Review Machine learning and multi-omics in precision medicine for ME/CFS, 2025, Huang....Armstrong

Reference #18 is A Treatise on the Principles and Practice of Medicine. Designed for the Use of practitioners and students of Medicine. Atlanta Med Surg J. 1867!
I don't think it is helpful suggesting that ME/CFS is such an exception from other diseases.

Think of sickle cell anaemia - it has symptoms of pain throughout the body, fatigue, infections, vision problems, diarrhoea. Prior to 1910 when it was first documented in western medicine, many people with the condition probably would have been in the same position as people with ME/CFS are in now in terms of there being little understanding and no treatment. There are lots of diseases that have symptoms in a range of body systems.



The idea of Figure 1 is really good. It summarises 'symptom manifestations and biological characterisation opportunities'.

A notable gap though is muscle fatiguability, which is a major and common symptom of ME/CFS. The Musculoskeletal heading has only

• muscular/joint pain
• muscle twitching
• hypermobility

I don't think we've seen much evidence yet to support muscle twitching and hypermobility as key symptoms of ME/CFS. Related to muscle fatiguability are a range of biological characterisation opportunities such as gait studies, eye muscle fatiguability studies and muscle electrical conduction studies - but none are listed in the figure.

Under Cardiovascular is

• Orthostatic hypotension
• Irregular heart beat
• Dizziness
• Chest pain

I'm not sure that I have seen irregular heart beat as an evidenced symptom of ME/CFS, or chest pain. I think high resting heart rate is a more commonly discussed symptom. And it's odd to single out orthostatic hypotension for inclusion, when really I think orthostatic intolerance is the symptom, and various sorts of oddities with blood pressure and heart rate are opportunities for biological characterisation.

There are probably more improvements that could be made to the figure e.g. blurred vision.

 

There are some good points made e.g.

The fluctuation of symptoms and therefore 'omics measurements

New technologies such as wearables, home testing, better quicker analysis

I don't think pacing is a treatment strategy and nor is support of various sorts. These are management strategies. They don't cure the disease. Again, it is important that the ME/CFS literature acknowledges that we don't have evidenced treatments. Even things like pain relief are not treatments of ME/CFS, they are treatments of pain or whatever.

Yeah, this is where I get concerned again. It's more of the 'there are treatments, it's just that no one treatment helps everyone - so we just need to work out how to match the treatments to the person better'.

There is not an 'urgent need for personalised treatment approaches that target the underlying biology of the individual' - that is not the first answer to a 'growing online community of ME/CFS patients sharing their self-medication experiences'. The urgent need is finding out what causes ME/CFS and doing quality trials to find a treatment that helps. You don't run before you can walk.

 

Reference 29 is
Kavyani B, Lidbury BA, Schloeffel R, Fisher PR, Missailidis D, Annesley SJ, et al. Could the kynurenine pathway be the key missing piece of myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) complex puzzle? Cell Mol Life Sci. 2022;79(8):412.
That was a bad paper. We talked about it here:
Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle?, 2022, Kavyani
The pharmacological treatment reported for fatigue was stimulants and vitamin and mineral supplements.

I'm conscious that these papers are being done by students. I'm grateful that they have decided to devote years of their lives to moving the understanding of ME/CFS forward. But, they and their supervisors need to be aware that if they are going to improve things for us, they need to get things right rather than confusing things further. The thing is, the paper isn't just about things like computational biology techniques, it's about a disease affecting people. Those of us with the disease want to see that the people we are relying on to find the answers both understand ME/CFS and care enough to get things right.

I think @Jonathan Edwards has a point when he suggests that not every review needs to be published. Either that or the supervisors need to put more time into improving the student's draft, polishing it for publication. Perhaps getting the student to post their draft here would be one way to get pre-publication feedback. It's annoying for everyone when criticism comes after publication.

 

Perhaps students in this situation could be encouraged to share their learning process and review writing process here, so we can give feedback before it reaches publication stage. They could do it on a members only thread if they don't want to make their learning process public.

We all want research students to do well both for themselves as they get stuck into the process of learning to be good researchers, and for pwME who will benefit from better quality research and publications.

 

That's why I suggested joining the forum before submitting their essay for publication. I think we have been quite helpful to students who ask questions and want to understand more, especially if they tell us what stage they are in learning. The problem comes when journals publish student essays, so we critique them by the same standard as we critique their professors.

I hope the student in this case will treat it as a learning experience, a tough one, but one that can help them become a better scientist.

Take into account also that forum threads are conversations between people with vastly varied backgrounds. Some of us get things wrong, some have illuminating insights. Part of learning is acquiring the knowledge and skills to distinguish between them.

 

There are two different things - the assumed trigger and the collection of symptoms.

People can meet ME/CFS criteria after a range of triggers, e.g. post-Q fever ME/CFS; post-EBV ME/CFS; post-SARS-1 ME/CFS; Post-COVID-19 ME/CFS. It's often useful to note the trigger, but ME/CFS is the syndrome.

Long Covid is simply the persistence of (new) symptoms for 3 months after Covid-19. For some people, that is loss of taste or smell. That obviously isn't ME/CFS. Neither is lung damage with persistent cough or kidney damage. Long Covid is the umbrella term for a range of health conditions thought to have been triggered by Covid-19.

Some people use Long Covid as a synonym for ME/CFS-like illness after Covid-19 (where not everyone exactly meets ME/CFS criteria, but fatigue is a core part of their illness), but I think that's too imprecise to be useful in science when others are using it to also mean all those other health consequences. If it is used in that way, it needs to be carefully defined, especially in scientific papers.

Yes, you can have ME/CFS and also have a persisting loss of taste or a persisting cough, for example, after Covid-19. But that isn't ME/CFS with a comorbidity of Long covid, it's ME/CFS with a comorbidity of e.g. ageusia or scarred lungs.

Some people who had ME/CFS get more severe after Covid-19. They will probably want to claim having Long Covid, as there can be more help for people with Long Covid than with ME/CFS. But, there is no co-morbidity there.

Many people who develop ME/CFS after January 2020 are likely to attribute it to Covid-19 regardless of the actual trigger and call it Long Covid, because there is more information and awareness out there about Long Covid for doctors and patients and there is more help for people with Long Covid. If that keeps happening, very few people will be labelled with new onset ME/CFS, maybe just some people who develop ME/CFS after another obvious infection such as EBV.

I think it is important that scientists bring clarity to the question of Long Covid. I think that usually means using other terms that are more accurate, or at least explaining what they mean when they use the term.

 

A number of us have recognised that it is hard on students to be subjected to public criticism and have tried with this team and others to establish ways for informed patients to provide private feedback before a paper is published. I personally spend time providing private feedback on studies for other teams. It is stressful to make these criticisms here; I worry that I'm not being considerate of the feelings of the PhD student. But, this isn't an essay submitted for a university class, it is a published paper.

Regardless of whether the paper is produced by a PhD student or not, published papers have consequences, it's hard to know ahead of time whether they will be trivial or not. We've seen that with the poor quality Kavyani paper, which is cited by this paper and which has contributed to the idea that there are useful treatments for people with ME/CFS, it's just that not everyone responds to all of them and we just don't know who responds to which one. That idea, and probably that paper, has contributed to a situation where people with ME/CFS, often encouraged by their doctors, spend a lot of money trying all sorts of treatments, some of them risky (edit - sometime even though preliminary studies showed no real benefit). The message has been picked up here and amplified further, with the suggestion that precision medicine will help identify which treatment will work for an individual.

And the paper is not just by the PhD student, it also bears the name of the leader of an important team working on ME/CFS research, a team that is a major part of the OMF fundraising machine. It's from a team that most of us recognise as one of the best teams working on ME/CFS out there. This paper and others published by them provide an indication of the attitudes and effort of all of those people. I believe it is reasonable and even important to express concern when their papers indicate that they hold some wrong ideas.

 

This section has some nice content.

I would have liked to see some discussion here about issues specific to ME/CFS that might affect the quality of analysis, as these things are questions we often have about studies and would be useful for new researchers coming into the field. So, perhaps reprising the issue of mis-diagnoses (with biases perhaps varying by location). So, you might get a systematic difference between ME/CFS cohorts from two different clinics and it can be very hard to know if it is the result of differences in the type of patient included in the cohort or due to differences in storage of the samples or of they way they were analysed.

Also, the difficulties around collecting samples from people with severe ME/CFS, and how this can affect the quality of the samples (e.g. does it take longer to get the samples processed?).

Perhaps these things are discussed later.

Reference #34 is
Huang K, Thomas N, Gooley PR, Armstrong CW. Systematic review of NMR-Based Metabolomics practices in Human Disease Research. Metabolites. 2022;12(10).
It sounds interesting; it's by most of the authors of this paper. We don't have a thread for it yet.

 

This section seems to me to be a useful introduction to the topic

Table 1 is a list of recent ME/CFS studies classifying big data. It is noticeable how small most of the samples are. The importance of validating the findings is stressed, by holding back a portion of the data for the validation test, and by replicating the finding using other data.