How to select trial participants with ME/CFS?

[jnmaciuch]

Even if the interviews are only thought of as a bonus, I still wonder if PEM might be too difficult a focus. You could get as many different descriptions as there are individuals, and have to commit a lot of time to trying to make sense of them vs your multi-omics results—or explaining why you couldn't. A doctoral programme's tough enough as it is without the risk of wandering into quicksand.

There are other questions which are just as interesting and potentially more amenable to answers. For instance, even if DecodeME provides real insights into the genetics of ME/CFS, it might not offer us much about male-female (as assigned at birth) differences. There have been hints of this in the research, including the findings on amino acid metabolism/ utilisation made by Fluge and Mella in about 2016, but they haven't been chased down. Could multi-omits tell us more?

Then there are the differences in results for mild/moderate and severely affected patients in recent papers. It doesn't appear to have been anticipated, yet the findings were there. Maybe it could be approached from the other end, actually starting with "Can I show differences between cohorts of mild/moderate and severe participants?".

They're important questions, and might have the potential to make more of a contribution than another look at PEM.

The idea would initially be at baseline w/o PEM—I’m fairly confident that at least some signature can be picked up outside of PEM.

I’m not married to this idea, I just sense that it might be a continuing problem even for finding a pathological mechanism if there’s no good way to select a relatively homogenous study group or identify subsets within a heterogenous study group.

Incidentally, the amino acid metabolism and utilization findings are driving my malate-aspartate shuttle pet theory, which I plan to keep pursuing. It’s just likely not going to be my PhD thesis since I’m in a lab with a computational focus—I’ll need another computationally focused project like a multi-omics analysis.

Unfortunately multi-omics is not well suited for hypothesis testing, so it would not be able to give me much more insight about any previous findings other than to just confirm them. But it is well suited for identifying existing patterns in the absence of a pathological mechanism