Recursive ensemble feature selection provides a robust mRNA expression signature for myalgic encephalomyelitis/chronic fatigue syndrome

Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disorder characterized by disabling fatigue. Several studies have sought to identify diagnostic biomarkers, with varying results. Here, we innovate this process by combining both mRNA expression and DNA methylation dat...

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Autores principales: Paula I. Metselaar, Lucero Mendoza-Maldonado, Andrew Yung Fong Li Yim, Ilias Abarkan, Peter Henneman, Anje A. te Velde, Alexander Schönhuth, Jos A. Bosch, Aletta D. Kraneveld, Alejandro Lopez-Rincon
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/d0baf6feb4464600ad1e82326571d72d
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Sumario:Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disorder characterized by disabling fatigue. Several studies have sought to identify diagnostic biomarkers, with varying results. Here, we innovate this process by combining both mRNA expression and DNA methylation data. We performed recursive ensemble feature selection (REFS) on publicly available mRNA expression data in peripheral blood mononuclear cells (PBMCs) of 93 ME/CFS patients and 25 healthy controls, and found a signature of 23 genes capable of distinguishing cases and controls. REFS highly outperformed other methods, with an AUC of 0.92. We validated the results on a different platform (AUC of 0.95) and in DNA methylation data obtained from four public studies on ME/CFS (99 patients and 50 controls), identifying 48 gene-associated CpGs that predicted disease status as well (AUC of 0.97). Finally, ten of the 23 genes could be interpreted in the context of the derailed immune system of ME/CFS.