A Network Medicine Approach to Investigating ME/CFS Pathogenesis in Severely Ill Patients: A Pilot Study, 2024, Hung, Davis, Xiao

Discussion in 'ME/CFS research' started by Dolphin, Sep 27, 2024.

  1. Dolphin

    Dolphin Senior Member (Voting Rights)

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    Now published - link
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    Preprint
    https://www.medrxiv.org/content/10.1101/2024.09.26.24314417v1

    A Network Medicine Approach to Investigating ME/CFS Pathogenesis in Severely Ill Patients: A Pilot Study

    Li-Yuan Hung, Chan-Shuo Wu, Chia-Jung Chang, Peng Li, Kimberly Hicks, Becky Taurog, Joshua J Dibble, Braxton Morrison, Chimere L Smith, Ronald W Davis, Wenzhong Xiao
    doi: https://doi.org/10.1101/2024.09.26.24314417


    Abstract

    This pilot study harnessed the power of network medicine to unravel the complex pathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

    By utilizing a network analysis on whole genome sequencing (WGS) data from the Severely Ill Patient Study (SIPS), we identified ME/CFS-associated proteins and delineated the corresponding network-level module, termed the SIPS disease module, together with its relevant pathways.

    This module demonstrated significant overlap with genes implicated in fatigue, cognitive disorders, and neurodegenerative diseases.

    Our pathway analysis revealed potential associations between ME/CFS and conditions such as COVID-19, Epstein-Barr virus (EBV) infection, neurodegenerative diseases, and pathways involved in cortisol synthesis and secretion, supporting the hypothesis that ME/CFS is a neuroimmune disorder.

    Additionally, our findings underscore a potential link between ME/CFS and estrogen signaling pathways, which may elucidate the higher prevalence of ME/CFS in females.

    These findings provide insights into the pathogenesis of ME/CFS from a network medicine perspective and highlight potential therapeutic targets.

    Further research is needed to validate these findings and explore their implications for improving diagnosis and treatment.

     
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  2. Hutan

    Hutan Moderator Staff Member

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    Ron Davis' lab, funding from OMF and the Patient-Led Collaborative

    We know that the body adapts to a lack of physical challenge - there is no need to produce high levels of cortisol if someone is sedentary at home. There is particularly no need to have a marked morning peak cortisol level if a person is not getting up and rushing about to get on with their day. So, give the strong likelihood that any differences from mean levels of healthy controls are just an environmental adaptation, I'll be interested to see if there is any genetic difference tied to low cortisol levels.

    These are small numbers. I mean, fair enough to look to see if there is some genetic story and a finding even in one person could be helpful in identifying a subset or misdiagnosis, but 'at least 2 patients' is a low bar. The abstract should have included the details of the sample size and how common the identified genes were in the sample.
     
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  3. Hutan

    Hutan Moderator Staff Member

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  4. Saz94

    Saz94 Senior Member (Voting Rights)

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    Yeah... hopefully the DECODE ME gene study should be more helpful given the large sample size.
     
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  5. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    Agree. Also could highlight the specific therapeutic targets in the abstract, and the last sentence of the abstract isn’t needed.
     
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  6. Murph

    Murph Senior Member (Voting Rights)

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    Small sample but they do also blend two other cohorts in and look for commonalities.

    This is not game-changing research or cure-finding research but it probably help tip the funding paradigm slightly in the direction of EBV and neuro issues.

    And when DecodeME comes out (suppposedly in August 2025) it will be useful to cross-reference this.
     
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  7. Andy

    Andy Retired committee member

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    That is when the project and funding ends, our aim is to publish results before then.
     
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  8. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights) Staff Member

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  9. Nightsong

    Nightsong Senior Member (Voting Rights)

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    Now published in Frontiers in Human Neuroscience:

    Link | PDF (open access)
     
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