Circulating cell-free RNA signatures for the characterization and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
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ABSTRACT:
PROVIDER: PRJNA1246570 | ENA |
REPOSITORIES: ENA
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Project description:Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) a debilitating multisystemic disease of unknown etiology, affecting thousands of individuals worldwide, still relies on ruling out medical problems leading to unexplained exertion for its diagnosis due to a complete lack of disease-specific biomarkers. Our group and other, have explored the potential value of microRNA profiles (miRNomes) as diagnostic tools for this disease. However, heterogeneity of participants, low numbers, the variety of samples assayed, and other pre-analytical variables, have hampered the identification disease-associated miRNomes. In this study, our team has evaluated, for the first time, ME/CFS miRNomes in PBMCs and EVs from severely ill patients recruited at the monographic UK ME biobank as a strategy to assess, using SOPs, blood fractions with optimal diagnostic power for a rapid translation of a miR-based diagnostic method into the clinic. Our results show that routine creatine kinase (CK) blood values, plasma EVs physical characteristics (including counts, size and zeta-potential), and a limited number of differentially expressed PBMC and EV miRNAs appear significantly associated with severe ME/CFS (p<0.05). Gene enrichment analysis points to epigenetic and neuroimmune dysregulated pathways, in agreement with previous reports. Population validation by a cost-effective approach limited to these few potentially discriminating variables remains.
2020-02-08 | GSE141770 | GEO
Project description:People living with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience heterogeneous and debilitating symptoms that lack sufficient biological explanation, compounded by the absence of accurate, noninvasive diagnostic tools. To address these challenges, we explored circulating cell-free RNA (cfRNA) as a blood-borne bioanalyte to monitor ME/CFS. cfRNA is released into the bloodstream during cellular turnover and reflects dynamic changes in gene expression, cellular signaling, and tissue-specific processes. We profiled cfRNA in plasma by RNA sequencing for 93 ME/CFS cases and 75 healthy sedentary controls, then applied machine learning to develop diagnostic models and advance our understanding of ME/CFS pathobiology. A generalized linear model with least absolute shrinkage selector operator regression trained on condition-specific signatures achieved a test-set AUC of 0.81 and an accuracy of 77%. Immune cfRNA deconvolution revealed differences in platelet-derived cfRNA between cases and controls, as well as elevated levels of plasmacytoid dendritic, monocyte, and T cell–derived cfRNA in ME/CFS. Biological network analysis further implicated immune dysfunction in ME/CFS, with signatures of cytokine signaling and T cell exhaustion. These findings demonstrate the utility of RNA liquid biopsy as a minimally invasive tool for unraveling the complex biology behind chronic illnesses.
2025-08-18 | GSE293840 | GEO
Project description:Assessing diagnosis value of miRNA from PBMCs and EVs in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
| PRJNA594654 | ENA
Project description:Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, potential interactions between DNA methylation and genetic background in relation to ME/CFS have not been examined. In this study we explored this association by characterizing the epigenetic (~480 thousand CpG loci) and genetic (~4.3 million SNPs) variation between cohorts of ME/CFS patients and healthy controls. We found significant associations of DNA methylation states in T-lymphocytes at several CpG loci and regions with ME/CFS phenotype. These methylation anomalies are in close proximity to genes involved with immune function and cellular metabolism. Finally, we found significant correlations of genotypes with methylation modifications associated with ME/CFS. The findings from this study highlight the role of epigenetic and genetic interactions in complex diseases, and suggest several genetic and epigenetic elements potentially involved in the mechanisms of disease in ME/CFS.
2020-08-25 | GSE156792 | GEO
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder that may occur following an infection, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit a cohort of post-infectious ME/CFS (PI-ME/CFS) volunteers (n=17) with matched healthy controls (n=21) to conduct deep clinical and biological phenotyping using an extensive battery of tests. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical deconditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
2023-12-22 | GSE251790 | GEO
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder that may occur following an infection, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit a cohort of post-infectious ME/CFS (PI-ME/CFS) volunteers (n=17) with matched healthy controls (n=21) to conduct deep clinical and biological phenotyping using an extensive battery of tests. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical deconditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
2024-01-24 | GSE254030 | GEO
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder that may occur following an infection, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit a cohort of post-infectious ME/CFS (PI-ME/CFS) volunteers (n=17) with matched healthy controls (n=21) to conduct deep clinical and biological phenotyping using an extensive battery of tests. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical deconditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
2023-10-31 | GSE245661 | GEO
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder that may occur following an infection, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit a cohort of post-infectious ME/CFS (PI-ME/CFS) volunteers (n=17) with matched healthy controls (n=21) to conduct deep clinical and biological phenotyping using an extensive battery of tests. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical deconditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
2023-12-22 | GSE251872 | GEO
Project description:Insights into the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) through metabolomic profiling of cerebrospinal fluid
2019-07-01 | MSV000084040 | GNPS
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multi-symptom illness characterized by debilitating fatigue and post-exertional malaise (PEM). Numerous studies have reported sex differences at the epidemiological, cellular, and molecular levels between male and female ME/CFS patients. To gain further insight into these sex-dependent changes, we evaluated differential gene expression by RNA-sequencing in 35 ME/CFS patients (24 female, 11 male) and 34 matched healthy control participants (21 female and 13 male) during and after an exercise challenge intended to provoke PEM. The effects of exertion in the male ME/CFS cohort highlighted pathways related to immune cell signaling (including IL-12) and NK cell cytotoxicity, while female ME/CFS patients did not have significant enough changes in gene expression to meet criteria for our study. Functional analysis during recovery from exercise showed that male ME/CFS patients had distinct changes in regulation of specific cytokine signals (including IL-1β). Female ME/CFS patients had significant alterations in gene networks related to cell stress, response to herpes viruses and NF-kβ signaling. The functional pathways and differentially expressed genes highlighted in this study provide insight into sex-specific predisposition and pathophysiology of ME/CFS.
2023-06-19 | GSE227375 | GEO