A network medicine approach to investigating ME/CFS pathogenesis in severely ill patients: a pilot study

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-associat...

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Main Authors: Li-Yuan Hung, Chan-Shuo Wu, Chia-Jung Chang, Peng Li, Kimberly Hicks, Joshua J. Dibble, Braxton Morrison, Chimere L. Smith, Ronald W. Davis, Wenzhong Xiao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Human Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnhum.2025.1509346/full
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author Li-Yuan Hung
Chan-Shuo Wu
Chia-Jung Chang
Peng Li
Kimberly Hicks
Joshua J. Dibble
Braxton Morrison
Chimere L. Smith
Ronald W. Davis
Wenzhong Xiao
author_facet Li-Yuan Hung
Chan-Shuo Wu
Chia-Jung Chang
Peng Li
Kimberly Hicks
Joshua J. Dibble
Braxton Morrison
Chimere L. Smith
Ronald W. Davis
Wenzhong Xiao
author_sort Li-Yuan Hung
collection DOAJ
description 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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publishDate 2025-02-01
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spelling doaj-art-c6991c93d23a4e8abe06c2d3965e14d52025-02-10T06:49:01ZengFrontiers Media S.A.Frontiers in Human Neuroscience1662-51612025-02-011910.3389/fnhum.2025.15093461509346A network medicine approach to investigating ME/CFS pathogenesis in severely ill patients: a pilot studyLi-Yuan Hung0Chan-Shuo Wu1Chia-Jung Chang2Peng Li3Kimberly Hicks4Joshua J. Dibble5Braxton Morrison6Chimere L. Smith7Ronald W. Davis8Wenzhong Xiao9Computational Research Center for Complex Chronic Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesComputational Research Center for Complex Chronic Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesME/CFS Collaborative Research Center, Stanford University School of Medicine, Palo Alto, CA, United StatesComputational Research Center for Complex Chronic Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesOpen Medicine Foundation, Agoura Hills, CA, United StatesComputational Research Center for Complex Chronic Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesComputational Research Center for Complex Chronic Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesPatient Led Research Collaborative, Washington, DC, United StatesME/CFS Collaborative Research Center, Stanford University School of Medicine, Palo Alto, CA, United StatesComputational Research Center for Complex Chronic Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesThis 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.https://www.frontiersin.org/articles/10.3389/fnhum.2025.1509346/fullnetwork medicineME/CFSchronic fatigue syndromeneuroimmunologyneurodegenerative diseasescognitive disorders
spellingShingle Li-Yuan Hung
Chan-Shuo Wu
Chia-Jung Chang
Peng Li
Kimberly Hicks
Joshua J. Dibble
Braxton Morrison
Chimere L. Smith
Ronald W. Davis
Wenzhong Xiao
A network medicine approach to investigating ME/CFS pathogenesis in severely ill patients: a pilot study
Frontiers in Human Neuroscience
network medicine
ME/CFS
chronic fatigue syndrome
neuroimmunology
neurodegenerative diseases
cognitive disorders
title A network medicine approach to investigating ME/CFS pathogenesis in severely ill patients: a pilot study
title_full A network medicine approach to investigating ME/CFS pathogenesis in severely ill patients: a pilot study
title_fullStr A network medicine approach to investigating ME/CFS pathogenesis in severely ill patients: a pilot study
title_full_unstemmed A network medicine approach to investigating ME/CFS pathogenesis in severely ill patients: a pilot study
title_short A network medicine approach to investigating ME/CFS pathogenesis in severely ill patients: a pilot study
title_sort network medicine approach to investigating me cfs pathogenesis in severely ill patients a pilot study
topic network medicine
ME/CFS
chronic fatigue syndrome
neuroimmunology
neurodegenerative diseases
cognitive disorders
url https://www.frontiersin.org/articles/10.3389/fnhum.2025.1509346/full
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