{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:32Z","timestamp":1792800032311,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"\n Objective<\/jats:title>\n Fibromyalgia (FM) is a complex autoimmune disorder characterized by widespread pain and fatigue, with significant diagnostic challenges due to the absence of specific biomarkers. This study aims to identify and validate potential genetic markers for FM to facilitate earlier diagnosis and intervention.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We analyzed gene expression data from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) associated with FM. Comprehensive enrichment analyses, including Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathways, were performed to elucidate the biological functions and disease associations of the candidate genes. We used the eXtreme Gradient Boosting (XGBoost) algorithm to develop a diagnostic model, which was validated using independent datasets.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Three genes, namely, dual-specificity tyrosine phosphorylation-regulated kinase 3\n (DYRK3)<\/jats:italic>\n , regulator of G protein signaling 17\n (RGS17),<\/jats:italic>\n and Rho guanine nucleotide exchange factor 37\n (ARHGEF37)<\/jats:italic>\n , were identified as key biomarkers for FM. These genes are implicated in critical processes such as ion homeostasis, cell signaling, and neurobiological functions, which are perturbed in FM. The diagnostic model demonstrated robust performance, with an area under the curve (AUC) of 0.8338 in the training set and 0.8178 in the validation set, indicating its potential utility in clinical settings.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The study successfully identifies three diagnostic biomarkers for FM, supported by both bioinformatics analysis and machine learning models. These findings could significantly improve diagnostic accuracy for FM, leading to better patient management and treatment outcomes.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fgene.2025.1535541","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T02:06:26Z","timestamp":1744855586000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of diagnostic biomarkers for fibromyalgia using gene expression analysis and machine learning"],"prefix":"10.3389","volume":"16","author":[{"given":"Fuyu","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunshen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiya","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingheng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cen","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.psc.2010.01.001","article-title":"The pathophysiology, diagnosis and treatment of fibromyalgia","volume":"33","author":"Arnold","year":"2010","journal-title":"Psychiatr. Clin. North Am."},{"key":"B2","unstructured":"data.table: extension of data.frame. R package version 1.15.4\n \n \n \n Barrett\n T.\n \n \n Dowle\n M.\n \n \n Srinivasan\n A.\n \n \n Gorecki\n J.\n \n \n Chirico\n M.\n \n \n Hocking\n T.\n \n \n \n 2024"},{"key":"B3","doi-asserted-by":"publisher","first-page":"176385","DOI":"10.1016\/j.ejphar.2024.176385","article-title":"Involvement of peripheral mast cells in a fibromyalgia model in mice","volume":"967","author":"Brum","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1097\/00002281-200103000-00005","article-title":"Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome","volume":"13","author":"Buskila","year":"2001","journal-title":"Curr. Opin. Rheumatol."},{"key":"B5","article-title":"_org.Hs.eg.db: genome wide annotation for Human_","author":"Carlson","year":"2024","journal-title":"R. package version"},{"key":"B6","unstructured":"xgboost: extreme Gradient Boosting. R package version 1.7.8.1\n \n \n \n Chen\n T.\n \n \n He\n T.\n \n \n Benesty\n M.\n \n \n Khotilovich\n V.\n \n \n Tang\n Y.\n \n \n Cho\n H."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1101\/2024.01.21.576131","article-title":"edgeR 4.0: powerful differential analysis of sequencing data with expanded functionality and improved support for small counts and larger datasets","author":"Chen","year":"","journal-title":"bioRxiv"},{"key":"B8","doi-asserted-by":"publisher","first-page":"907","DOI":"10.4065\/mcp.2011.0206","article-title":"The science of fibromyalgia","volume":"86","author":"Clauw","year":"2011","journal-title":"Mayo Clin. Proc."},{"key":"B9","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1186\/ar2443","article-title":"Biology and therapy of fibromyalgia. Evidence-based biomarkers for fibromyalgia syndrome","volume":"10","author":"Dadabhoy","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","article-title":"GEOquery: a bridge between the gene expression omnibus (GEO) and BioConductor","volume":"23","author":"Davis","year":"2007","journal-title":"Bioinformatics"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0304-3959(00)00490-5","article-title":"The role of neuroinflammation and neuroimmune activation in persistent pain","volume":"90","author":"DeLeo","year":"2001","journal-title":"Pain"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1002\/cbic.202000740","article-title":"Fragment-based nuclear magnetic resonance screen against a regulator of G protein signaling identifies a binding \u201chot spot\u201d","volume":"22","author":"Hayes","year":"2021","journal-title":"Chembiochem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.3390\/biomedicines12071543","article-title":"Fibromyalgia: a review of the pathophysiological mechanisms and multidisciplinary treatment strategies","volume":"12","author":"Jurado-Priego","year":"","journal-title":"Biomedicines"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.3390\/biomedicines12071543","article-title":"Fibromyalgia: a review of the pathophysiological mechanisms and multidisciplinary treatment strategies","volume":"12","author":"Jurado-Priego","year":"","journal-title":"Biomedicines"},{"key":"B15","article-title":"Factoextra: extract and visualize the results of multivariate data analyses","author":"Kassambara","year":"2020","journal-title":"R. package version 1.0.7"},{"key":"B16","article-title":"ROCit: performance assessment of binary classifier with visualization","author":"Khan","year":"2024","journal-title":"R. package version 2.1.2"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.3390\/ijms22062982","article-title":"Dual specificity kinase DYRK3 promotes aggressiveness of glioblastoma by altering mitochondrial morphology and function","volume":"22","author":"Kim","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v028.i05","article-title":"Building predictive models in R using the caret package","volume":"28","author":"Kuhn","year":"2008","journal-title":"J. Stat. Softw."},{"key":"B19","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.molbrainres.2003.11.014","article-title":"Selective expression of regulators of G-protein signaling (RGS) in the human central nervous system","volume":"122","author":"Larminie","year":"2004","journal-title":"Brain Res. Mol. Brain Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v025.i01","article-title":"FactoMineR: an R package for multivariate analysis","volume":"25","author":"Le","year":"2008","journal-title":"J. Stat. Softw."},{"key":"B21","doi-asserted-by":"publisher","first-page":"167301","DOI":"10.1016\/j.bbadis.2024.167301","article-title":"Role of mitochondrial dysfunction and biogenesis in fibromyalgia syndrome: molecular mechanism in central nervous system","volume":"1870","author":"Marino","year":"2024","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"5620","DOI":"10.1007\/s12035-016-0095-9","article-title":"High-intensity swimming exercise decreases glutamate-induced nociception by activation of G-protein-coupled receptors inhibiting phosphorylated protein kinase A","volume":"54","author":"Martins","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"B23","unstructured":"shapviz: SHAP Visualizations. R package version 0.9.5\n \n \n \n Mayer\n M.\n \n \n \n 2024"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.18129\/B9.bioc","article-title":"GSEABase: gene set enrichment data structures and methods","author":"Morgan","year":"2024"},{"key":"B25","article-title":"tibble: Simple data frames","author":"M\u00fcller","year":"2023","journal-title":"R. package version 3.2.1"},{"key":"B26","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/1471-2105-12-77","article-title":"pROC: an open-source package for R and S+ to analyze and compare ROC curves","volume":"12","author":"Robin","year":"2011","journal-title":"BMC Bioinforma."},{"key":"B27","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1097\/j.pain.0000000000001122","article-title":"Inflammation in the pathophysiology of neuropathic pain","volume":"159","author":"Sommer","year":"2018","journal-title":"Pain"},{"key":"B28","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.berh.2010.01.010","article-title":"Peripheral pain mechanisms in chronic widespread pain","volume":"25","author":"Staud","year":"2011","journal-title":"Best. Pract. Res. Clin. Rheumatol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1249\/MSS.0000000000002293","article-title":"Increased anandamide and decreased pain and depression after exercise in fibromyalgia","volume":"52","author":"Stensson","year":"2020","journal-title":"Med. Sci. Sports Exerc"},{"key":"B30","unstructured":"R package corrplot: visualization of a correlation matrix\n \n \n \n Taiyun\n W.\n \n \n Simko\n V.\n \n \n \n 2024"},{"key":"B31","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jocn.2019.04.029","article-title":"Can aberrant spinal nociception be a marker of chronicity of pain in fibromyalgia syndrome?","volume":"65","author":"Tanwar","year":"2019","journal-title":"J. Clin. Neurosci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"353","DOI":"10.3389\/fncel.2019.00353","article-title":"Mast cells, neuroinflammation and pain in fibromyalgia syndrome","volume":"13","author":"Theoharides","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v021.i12","article-title":"Reshaping data with the reshape package","volume":"21","author":"Wickham","year":"2007","journal-title":"J. Stat. Softw."},{"key":"B34","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: elegant graphics for data analysis","author":"Wickham","year":"2016"},{"key":"B35","article-title":"_stringr: Simple, consistent wrappers for common string operations_","author":"Wickham","year":"2023","journal-title":"R. package version 1.5.1"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"_Journal Open Source Software_"},{"key":"B37","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"B38","article-title":"Ggsci: scientific journal and sci-fi themed color palettes for ggplot2","author":"Xiao","year":"2024","journal-title":"R. package version 3.2.0"},{"key":"B39","doi-asserted-by":"publisher","first-page":"3292","DOI":"10.1038\/s41596-024-01020-z","article-title":"Using clusterProfiler to characterize multiomics data","volume":"19","author":"Xu","year":"2024","journal-title":"Nat. Protoc."},{"key":"B40","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS A J. Integr. Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"687975","DOI":"10.3389\/fimmu.2021.687975","article-title":"IOBR: multi-omics Immuno-Oncology Biological Research to decode tumor microenvironment and signatures","volume":"12","author":"Zeng","year":"2021","journal-title":"Front. Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1186\/s13046-022-02441-y","article-title":"ARHGEF37 overexpression promotes extravasation and metastasis of hepatocellular carcinoma via directly activating Cdc42","volume":"41","author":"Zhang","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1535541\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T02:06:30Z","timestamp":1744855590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1535541\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":42,"alternative-id":["10.3389\/fgene.2025.1535541"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2025.1535541","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,17]]},"article-number":"1535541"}}