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

I don't see it that way. This research group led by Chris Armstrong has been researching ME/CFS biology for some years, and show a good understanding of the difficulities of finding the cause of ME/CFS.

The social and behavioural bit puzzled me too. I'm hoping they simply mean that diagnosis includes asking the patient about the effects on their symptoms of different kinds of activity. Pacing is a behavioural strategy for managing ME/CFS to avoid PEM.

I suspect they are right that we need much bigger samples across multiple omics, which can only be analysed with the help of computer algorithms.

 

Interesting idea. Typing speed also depends on what I'm typing about.
Factors affecting my typing speed and number of corrections I need to make include
- fatiguablity - gets slower if I go on too long - both cognitive and physical.
- what else I've done that week, day, hour and how close to crashed I am
- the subject matter and whether it requires a lot of thought or I'm just rambling or copy typing
- whether I'm touch typing on my laptop or one finger typing on my phone.
- mistake rate increases markedly as I fatigue, if pushing when crashed, understanding the words on the screen and being able to spell them deteriorates
- overall quantity of typing may not directly relate to state of health - also depends on whether there's anything I want to say, and what else I'm doing

So it's a complex picture, but I think could be useful. Perhaps it needs to be narrowed down to something like assessing typing speed and error rate on a set task. Combining and or correlating it with steps, time with feet on the floor, resting heart rate, HRV might be interesting.

 

My posts definitely tend to get longer and more wordy when I’ve got to my limits. I often struggle to realise this until I stop typing and realise I’ve been rambling. It takes quite a bit of concentration to keep to the point.

 

Me too. Members might not believe this, given how much I post, but I quite often delete my long incoherent rambles without posting them.

 

I'm not sure what this sentence is saying.

'Complex' can be a code word for 'biopsychosocial' and 'psychosomatic'. Also, we don't really know that ME/CFS is complex, it's just that we don't understand it yet.

'Multifaceted' can be read as 'biopsychosocial' also - as in, 'yes there was a biological trigger but it is perpetuated by behavioural factors'. What multiple facets are being referred to here?

'Defies simplistic characterisation' also can be read as 'biopsychosocial' and suggests that ME/CFS has been characterised, just not simply. To date, that's not true. I'm not a fan of personifying the disease by suggesting it is defiant either.

If the authors meant when they described ME/CFS as 'complex, multifaceted, and defying simplistic characterisation' that it 'has many symptoms' and 'no one understands what causes it yet', why not just say something closer to that? Or was something else meant?
Probably you don't want to say 'researchers are currently resorting to models with large numbers of parameters, that are of questionable validity, in order to separate their usually way too small ME/CFS sample from their healthy controls, and these efforts are poorly replicated'.

Again, it's not clear what is being said here. There's a lack of precision in the sentence. Traditional approaches to treating ME/CFS are GET and CBT. They have not fallen short due to the condition's heterogeneity and lack of validated biomarkers. The sentence as it stands suggests that there are treatments and that they are sometimes useful. There is no evidence that those treatments work for anyone with any sort of CFS or ME/CFS diagnosis. Suggesting that there are effective treatments is wrong and problematic. We need to be saying clearly 'there are no evidence-based treatments for ME/CFS'.


Yes, I know this team means well and is doing good things. But those issues with the first two sentences of the abstract suggest a lack of care to get things right.

The abstract calls for 'collaborative data-sharing initiatives in the endeavour to unravel the biological intricacies of ME/CFS', which is great. But, did this project team include one or more people with ME/CFS familiar with the politics and the literature who could share what they know and help ensure that the many land mines of ME/CFS were not stepped on?

 

But I'm not clear what the word 'complex' is saying there -
1. that it's difficult to work out the cause, or
2. that there are many factors contributing to the disease (including possibly psychological ones), or
3. that the disease has many interacting parts, or
4. that there are lots of symptoms, or
5. something else?
Why not use a word that makes your meaning clear?

If 'complex' is being used to say that we don't understand it, why not say 'poorly understood'? Then you avoid the problematic 'complex' word. By using 'complex' you also give governments and funders and researchers an excuse, i.e. the reason millions of people don't have a treatment for a debilitating disease is because 'it's really really complicated', whereas a substantial part of the problem is that there has not been nearly enough effort and funds expended on finding the answers.

 

Introduction
I'm continuing to get the feeling that the text is just a bit 'off'; it's not tight.

This seems to at once be saying things that are vaguely obvious but are also unevidenced. In some respects, doesn't every chronic illness evolve and perpetuate from a combination of biological and environmental determinants? In what way is ME/CFS different?

In this sentence, it isn't just one physiological response, but a range of them. Reference 2 is the ICC criteria, which is an odd criteria to choose here. The sentence makes it seems as though all of those symptoms manifest in everyone with ME/CFS, all the time. This paper also talks about fatigue lasting for 3 months or longer, but the ICC does not give a time requirement and does not mention 3 months:

So the authors of this paper seem to have just made up the requirement for three months of idiopathic fatigue themselves.

Saying 'the exact biological mechanism that results in a chronic ME/CFS state remains unidentified' suggests that the biological mechanism is mostly known. I don't think we can say that. It could be viral persistence, it could be autoimmunity, it could be something else entirely. If we can't even point with certainty to a broad description, I don't think it's reasonable to talk about 'exact biological mechanisms'. As @oldtimer suggests, it is probably best to just be upfront that we don't know.
Reference #7 is

That was that rambling paper about Whitney, i.e about one person. I don't believe that that should be being cited as evidence of immunological anomalies in ME/CFS. I don't know if it was cited due to this team being part of the OMF group?

The way that sentence is phrased, it is unclear if the authors are recommending that ME/CFS is considered as a cluster of related, but distinct pathophysiological constructs versus one disease that goes through a progression of stages or if they are just saying 'here are two contrasting views'. I don't think anyone would argue that there are not substantial levels of misdiagnosis in people with a label of ME/CFS.
'pathophysiological constructs'? Who is doing the constructing? Why not use 'diseases' or 'disorders'? Why tell us that it's a reductionist view - when they also tell us that the view is that there is a singular entity? You can't get much lower than 1 and still have something. And we know, ME/CFS doesn't follow set stages of progression. Not everyone ends up severe, and some people who start out severe improve to mild. The concept of one broad disease does not necessarily require the idea that the disease progresses. I'm probably not explaining well, but I don't think people who know ME/CFS well would write a sentence like that.

I don't disagree with the point they are making, that the range of expressions of ME/CFS may be partly due host differences. But, long Covid is not really proof of that. We know that Long Covid is an umbrella term covering all sorts of illnesses, including things like lung damage, so some people don't have an ME/CFS-like illness at all.

The odd sentence that is a bit loose would be fine; it just might be different interpretations or something. But, there are so many sentences that aren't clear or quite logical. The paper needed a good proof-read.

 

I don't believe that there are laboratory tests of even some utility in positively diagnosing ME/CFS, never mind 'definitive'.

Again, the authors don't seem to have recognised that long Covid is simply the existence of new persistent symptoms after a Covid-19 infection. If someone meets the criteria for ME/CFS after a Covid-19 infection, they have ME/CFS. Someone with ME/CFS after a Covid-19 infection doesn't really have 'long Covid' as a co-morbidity, anymore than someone with ME/CFS after EBV has 'long EBV' as a co-morbidity.

It is not clear why some non-ME/CFS post-Covid pathology such as lung damage or kidney damage is less of a problem in terms of muddying the multi-omic waters than an undiagnosed rheumatic disease. I think the point that there is a high risk of misdiagnosis in people with ME/CFS labels could have been made more simply and compellingly.

 

I am skeptical about the concept of precision medicine when applied to ME/CFS right now. It works in oncology because clinicians have moved beyond 'cancer' to knowing specific types of cancer and how to treat them. And there is information about how people with specific genes respond to different treatments. Basically, it works because so much is known, and oncologists are now fine-tuning the knowledge.

Whereas, with ME/CFS, we are still at the 'a trigger might cause some sort of unknown physiological reaction that causes a chronic state as a result of some unknown mechanism'. I don't think you can usefully do 'precise', without doing 'accurate' first. For our disease, I think precision medicine is a trendy buzzword. Perhaps this paper helps build a case for ME/CFS research being eligible for pots of 'precision medicine' funding, in which case, all power to the authors. But, other than that, I'm not yet sure why 'precision medicine' is in the title of this paper. Maybe it will become clear.


The next paragraph seems to essentially say what I have said:

That is, first we need to get an idea of what the ME/CFS pathology is.

But, that's in contrast to the sentences in the abstract:

Something has to exist before you transform it.

I've seen 'precision medicine' used to describe things as diverse as wastewater testing for Covid-19, genetic testing of newborns and apps that are supposed to help people quit smoking or lose weight. It can be used for anything technological. It's a vague term that I think is best avoided. Terms that really mean something, like 'computational biology' and 'individualised treatment' are better.