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    Development and validation of blood-based diagnostic biomarkers for [ME/CFS] using EpiSwitch®… 2025, Hunter et al. (Oxford Biodynamics)

    Knowing nothing about 3d-genomics (and being a non-scientist), I found this YouTube resource really helpful and easy to follow:
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    Development and validation of blood-based diagnostic biomarkers for [ME/CFS] using EpiSwitch®… 2025, Hunter et al. (Oxford Biodynamics)

    Quite apart from all the important (and valid) study-design and statistical issues raised above, the comment that really stands out for me is: The media hype is staggeringly inappropriate.
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    Unphosphorylated ISGF3 drives constitutive expression of interferon-stimulated genes to protect against viral infections, Wang et al. (2017)

    Thanks for that clear explanation. So this abstract statement: poses more questions than answers.
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    Unphosphorylated ISGF3 drives constitutive expression of interferon-stimulated genes to protect against viral infections, Wang et al. (2017)

    What causes the "...simultaneous overexpression of all ISGF3 components..."?
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    Trial Report Feasibility and tolerability of dual-target [rTMS] for treatment of [ME/CFS]: An open label pilot study, 2025, Corlier et al

    What do we think of the "Fatigue Severity Scale"? It seemingly was constucted by some doctors in 1989 to track/diagnose MS and SLE. To equally weight 9 questions like "1. My motivation is lower when I am fatigued. 2. Exercise brings on my fatigue. 3. I am easily fatigued. " seems not very...
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    Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and ME/CFS, Haffke, Scheibenbogen et al, 2022

    Yet this 2021 study says
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    Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and ME/CFS, Haffke, Scheibenbogen et al, 2022

    The EndoPAT device seems to no longer be in production, and this 2012 paper had doubts about what it was actually measuring (although perhaps they addressed issues for the thread paper) In any case, I agree with:
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    Trial Report Plasma cell targeting with the anti-CD38 antibody daratumumab in ME/CFS -a clinical pilot study, 2025, Fluge et al

    Seems like mitochondria transfer can occur on a PEM-like timescale.
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    Comparing different acupuncture methods for the treatment of chronic fatigue syndrome: a systematic review and network meta-analysis, 2025, Li et al

    silly old "western medicine" the corresponding author.
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    Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome, Maes et al, 2015

    You are right - the important tests are surely for differences in proportions of these subsets corrected for age and sex; as you say:
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    Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome, Maes et al, 2015

    The RESULTS page says gender and age (and interaction diagnosis * gender) were GLM explanatory:
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    Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Fluge, Mella et al 2020

    Their p<0.001 significance threshold seems to be a heuristic: Section 3.1 says HLA-C did not quite reach this threshold:
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    List of causation hypothesis for follow up after DecodeME

    Similarities with tinnitus, where (in the most common pathway) loss of afferent signals (caused by damaged hair cells for some frequencies) encourage auditory pathway neurons that normally process these frequencies, and/or neighboring cells alert to this lack of signalling, may spontaneously...
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    Preprint Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, DecodeMe Collaboration

    Fantastic - thanks so much. The paper confused me: it wasn't clear what "these" referred to.
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    Preprint Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, DecodeMe Collaboration

    Would you be able to answer my earlier question to Prof Ponting: This non-scientist's understanding would benefit from knowing the variables involved in the gene-set analyses: Z = B0 + C1.B1 + ... + CnBn + e ... is Z the 13 gene-analysis ones, or is it all 18k? ... is C1 a binary 0/1 for...
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    Preprint Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, DecodeMe Collaboration

    This non-scientist's understanding would benefit from knowing the variables involved in the gene-set analyses: Z = B0 + C1.B1 + ... + CnBn + e
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    MAGMA: Generalized Gene-Set Analysis of GWAS Data 2025 de Leeuw et al

    Great @Andy - thanks so much - this non-scientist has been toiling over the MAGMA analysis. The paper above is really good and this post and another from @forestglip really nails it.
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    Preprint Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, DecodeMe Collaboration

    Thanks so much. Presumably the vast non-coding genome regions would contain very few of the study's GWAS genotyped markers, so that the "Phasing and genotype imputation" genotyping steps would not not impute anything statistically reliable.
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    Preprint Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, DecodeMe Collaboration

    How are we to reconcile the somewhat different genes and tissues of: Fig. 3. MAGMA gene-tissue analysis shows statistically significant enrichment of ME/CFS-related genes in all 13 brain tissues. Fig. 4: Approximate Bayes factor posterior probability (PPH4) that mRNA expression and ME/CFS...
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    Preprint Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, DecodeMe Collaboration

    You are (way) ahead of me - I was reading the original 2015 MAGMA paper where the gene-set variables are just 0/1 although those authors point out "The variables C1, C2, . . ., in this generalized gene-set analysis model can reflect any gene property, from the binary indicators used for the...
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