{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:21:56Z","timestamp":1790295716123,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brain Research New Zealand"},{"name":"Sir Charles Hercus Fellowship (from the Health Research Council of New Zealand)"},{"name":"ANZMES"},{"name":"Marsden Fund"},{"name":"NZ ME\/CFS national advisory society"},{"name":"ME\/CFS families"},{"name":"University of Otago"},{"name":"Royal Society NZ"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Post-viral conditions, Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) and Long COVID (LC), share &gt; 95% of their symptoms, but the connection between disturbances in their underlying molecular biology is unclear. This study investigates DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from patients with ME\/CFS, LC, and healthy controls (HC). Reduced Representation Bisulphite Sequencing (RRBS) was applied to the DNA of age- and sex-matched cohorts: ME\/CFS (n = 5), LC (n = 5), and HC (n = 5). The global DNA methylomes of the three cohorts were similar and spread equally across all chromosomes, except the sex chromosomes, but there were distinct minor changes in the exons of the disease cohorts towards more hypermethylation. A principal component analysis (PCA) analysing significant methylation changes (p &lt; 0.05) separated the ME\/CFS, LC, and HC cohorts into three distinct clusters. Analysis with a limit of &gt;10% methylation difference and at p &lt; 0.05 identified 214 Differentially Methylated Fragments (DMF) in ME\/CFS, and 429 in LC compared to HC. Of these, 118 DMFs were common to both cohorts. Those in promoters and exons were mainly hypermethylated, with a minority hypomethylated. There were rarer examples with either no change in methylation in ME\/CFS but a change in LC, or a methylation change in ME\/CFS but in the opposite direction in LC. The differential methylation in a number of fragments was significantly greater in the LC cohort than in the ME\/CFS cohort. Our data reveal a generally shared epigenetic makeup between ME\/CFS and LC but with specific, distinct changes. Differences between the two cohorts likely reflect the stage of the disease from onset (LC 1 year vs. ME\/CFS 12 years), but specific changes imposed by the SARS-CoV-2 virus in the case of the LC patients cannot be discounted. These findings provide a foundation for further studies with larger cohorts at the same disease stage and for functional analyses to establish clinical relevance.<\/jats:p>","DOI":"10.3390\/ijms26146631","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T12:46:33Z","timestamp":1752237993000},"page":"6631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparing DNA Methylation Landscapes in Peripheral Blood from Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome and Long COVID Patients"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6072-5926","authenticated-orcid":false,"given":"Katie","family":"Peppercorn","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9538-3415","authenticated-orcid":false,"given":"Sayan","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina D.","family":"Edgar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2145-3493","authenticated-orcid":false,"given":"Peter A.","family":"Stockwell","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9615-5896","authenticated-orcid":false,"given":"Euan J.","family":"Rodger","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7276-2248","authenticated-orcid":false,"given":"Aniruddha","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6971-7734","authenticated-orcid":false,"given":"Warren P.","family":"Tate","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","unstructured":"WHO (2025, April 03). COVID-19 Cases, World. Available online: https:\/\/data.who.int\/dashboards\/covid19\/cases."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tate, W.P., Walker, M.O.M., Peppercorn, K., Blair, A.L.H., and Edgar, C.D. (2023). Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome and Long COVID. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065124"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41579-022-00846-2","article-title":"Long COVID: Major findings, mechanisms and recommendations","volume":"23","author":"Davis","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","unstructured":"Goldowitz, I., Worku, T., Brown, L., and Fineberg, H.V. (2024). A Long COVID Definition: A Chronic, Systemic Disease State with Profound Consequences, National Academies Press (US)."},{"key":"ref_5","unstructured":"Collins, F.S. (2025, April 01). NIH Launches New Initiative to Study \u201cLong COVID\u201d, Available online: https:\/\/www.nih.gov\/about-nih\/who-we-are\/nih-director\/statements\/nih-launches-new-initiative-study-long-covid."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1136\/bmj.2.5050.895","article-title":"An Outbreak of encephalomyelitis in the Royal Free Hospital Group, London, in 1955","volume":"2","author":"Staff","year":"1957","journal-title":"Br. Med. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1001\/archinte.1992.00400200049009","article-title":"Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome","volume":"152","author":"Levine","year":"1992","journal-title":"Arch. Intern. Med."},{"key":"ref_8","unstructured":"Shepherd, C., Chaudhuri, A., Association, M., Association, M.E., and Society, A.N.Z.M. (2013). ME\/CFS\/PVFS: An Exploration of the Key Clinical Issues, ME Association."},{"key":"ref_9","unstructured":"ME-Pedia (2025, May 10). Millions Missing Protests. Available online: https:\/\/me-pedia.org\/wiki\/Millions_Missing_protests."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tate, W., Walker, M., Sweetman, E., Helliwell, A., Peppercorn, K., Edgar, C., Blair, A., and Chatterjee, A. (2022). Molecular Mechanisms of Neuroinflammation in ME\/CFS and Long COVID to Sustain Disease and Promote Relapses. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.877772"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1001\/jama.2024.11370","article-title":"Evidence Mounts That About 7% of US Adults Have Had Long COVID","volume":"332","author":"Fang","year":"2024","journal-title":"JAMA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1056\/NEJMoa2403211","article-title":"Postacute Sequelae of SARS-CoV-2 Infection in the Pre-Delta, Delta, and Omicron Eras","volume":"391","author":"Xie","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1186\/s12967-022-03815-8","article-title":"Genetic risk factors for ME\/CFS identified using combinatorial analysis","volume":"20","author":"Das","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1186\/s12967-023-04588-4","article-title":"Genetic risk factors for severe and fatigue dominant long COVID and commonalities with ME\/CFS identified by combinatorial analysis","volume":"21","author":"Taylor","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102107","DOI":"10.1016\/j.eclinm.2023.102107","article-title":"Clinical phenotypes and quality of life to define post-COVID-19 syndrome: A cluster analysis of the multinational, prospective ORCHESTRA cohort","volume":"62","author":"Gentilotti","year":"2023","journal-title":"eClinicalMedicine"},{"key":"ref_16","first-page":"100022","article-title":"What Long COVID investigators can learn from four decades of ME\/CFS research","volume":"4","author":"Jason","year":"2023","journal-title":"Brain Behav. Immun. Integr."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Horwitz, L.I., Thaweethai, T., Brosnahan, S.B., Cicek, M.S., Fitzgerald, M.L., Goldman, J.D., Hess, R., Hodder, S.L., Jacoby, V.L., and Jordan, M.R. (2023). Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0285351"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.molmed.2021.06.002","article-title":"Insights from myalgic encephalomyelitis\/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome","volume":"27","author":"Komaroff","year":"2021","journal-title":"Trends Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1126\/science.abo1261","article-title":"Understanding myalgic encephalomyelitis","volume":"377","year":"2022","journal-title":"Science"},{"key":"ref_20","unstructured":"Komaroff, A.L. (2025, June 07). MECFS and Long COVID: Emerging Similarities and Why It Matters. Available online: https:\/\/www.youtube.com\/watch?v=AbVMvRS-a7Yc."},{"key":"ref_21","first-page":"1179","article-title":"Post-exertional malaise among people with long COVID compared to myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS)","volume":"74","author":"Vernon","year":"2023","journal-title":"Work"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Peppercorn, K., Edgar, C.D., Kleffmann, T., and Tate, W.P. (2023). A pilot study on the immune cell proteome of long COVID patients shows changes to physiological pathways similar to those in myalgic encephalomyelitis\/chronic fatigue syndrome. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-49402-9"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e183810","DOI":"10.1172\/jci.insight.183810","article-title":"Immune exhaustion in ME\/CFS and long COVID","volume":"9","author":"Rudd","year":"2024","journal-title":"JCI Insight"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s13148-020-00960-z","article-title":"Changes in DNA methylation profiles of myalgic encephalomyelitis\/chronic fatigue syndrome patients reflect systemic dysfunctions","volume":"12","author":"Helliwell","year":"2020","journal-title":"Clin. Epigenetics"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Helliwell, A.M., Stockwell, P.A., Edgar, C.D., Chatterjee, A., and Tate, W.P. (2022). Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome. Int. J. Mol. Sci., 23.","DOI":"10.1101\/2022.02.24.22270912"},{"key":"ref_26","first-page":"228","article-title":"Methylation Profile of CD4+ T Cells in Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis","volume":"5","author":"Brenu","year":"2014","journal-title":"J. Clin. Cell. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"de Vega, W.C., Vernon, S.D., and McGowan, P.O. (2014). DNA methylation modifications associated with chronic fatigue syndrome. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104757"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.2217\/epi-2017-0106","article-title":"The epigenetic landscape of myalgic encephalomyelitis\/chronic fatigue syndrome: Deciphering complex phenotypes","volume":"9","author":"McGowan","year":"2017","journal-title":"Epigenomics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"539","DOI":"10.2217\/epi-2017-0150","article-title":"Integration of DNA methylation & health scores identifies subtypes in myalgic encephalomyelitis\/chronic fatigue syndrome","volume":"10","author":"Erdman","year":"2018","journal-title":"Epigenomics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1080\/15592294.2018.1549769","article-title":"Genome-epigenome interactions associated with Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"13","author":"Herrera","year":"2018","journal-title":"Epigenetics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e70003","DOI":"10.1002\/cpz1.70003","article-title":"DMAP2: A Pipeline for Analysis of Whole-Genome-Scale DNA Methylation Sequencing Data","volume":"4","author":"Stockwell","year":"2024","journal-title":"Curr. Protoc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1534\/genetics.116.195594","article-title":"Trends in DNA Methylation with Age Replicate Across Diverse Human Populations","volume":"206","author":"Gopalan","year":"2017","journal-title":"Genetics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ajhg.2018.07.006","article-title":"IRF2BPL Is Associated with Neurological Phenotypes","volume":"103","author":"Marcogliese","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.freeradbiomed.2020.09.016","article-title":"Structure and functions of cellular redox sensor HSCARG\/NMRAL1, a linkage among redox status, innate immunity, DNA damage response, and cancer","volume":"160","author":"Zang","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1161\/ATVBAHA.120.314252","article-title":"Galectin-3 Identifies a Subset of Macrophages With a Potential Beneficial Role in Atherosclerosis","volume":"40","author":"Somerville","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1093\/hmg\/ddaa166","article-title":"SLC38A8 mutations result in arrested retinal development with loss of cone photoreceptor specialization","volume":"29","author":"Kuht","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1038\/s41467-018-03544-x","article-title":"Structure of Schlafen13 reveals a new class of tRNA\/rRNA- targeting RNase engaged in translational control","volume":"9","author":"Yang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1261\/rna.060517.116","article-title":"A genetic screen implicates a CWC16\/Yju2\/CCDC130 protein and SMU1 in alternative splicing in Arabidopsis thaliana","volume":"23","author":"Kanno","year":"2017","journal-title":"Rna"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12192-009-0127-8","article-title":"The small heat shock protein, HSPB6, in muscle function and disease","volume":"15","author":"Dreiza","year":"2010","journal-title":"Cell Stress Chaperones"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Krueger, S., Bernhardt, A., Kalinski, T., Baldensperger, M., Zeh, M., Teller, A., Adolf, D., Reinheckel, T., Roessner, A., and Kuester, D. (2013). Induction of premalignant host responses by cathepsin x\/z-deficiency in Helicobacter pylori-infected mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070242"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1021\/bi00435a059","article-title":"Characterization and differential expression of human vascular smooth muscle myosin light chain 2 isoform in nonmuscle cells","volume":"28","author":"Kumar","year":"1989","journal-title":"Biochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1124\/mol.62.3.485","article-title":"Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit","volume":"62","author":"Qin","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"34002","DOI":"10.1074\/jbc.M803957200","article-title":"FGD2, a CDC42-specific exchange factor expressed by antigen-presenting cells, localizes to early endosomes and active membrane ruffles","volume":"283","author":"Huber","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"13364","DOI":"10.1523\/JNEUROSCI.0230-14.2014","article-title":"EOL-1, the homolog of the mammalian Dom3Z, regulates olfactory learning in C. elegans","volume":"34","author":"Shen","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e2006476118","DOI":"10.1073\/pnas.2006476118","article-title":"The Parkinson\u2019s disease-associated gene ITPKB protects against \u03b1-synuclein aggregation by regulating ER-to-mitochondria calcium release","volume":"118","author":"Apicco","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9240","DOI":"10.1073\/pnas.0913748107","article-title":"Kif26b, a kinesin family gene, regulates adhesion of the embryonic kidney mesenchyme","volume":"107","author":"Uchiyama","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5702","DOI":"10.1038\/s41467-021-25846-3","article-title":"CHARGE syndrome protein CHD7 regulates epigenomic activation of enhancers in granule cell precursors and gyrification of the cerebellum","volume":"12","author":"Reddy","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1038\/sj.onc.1203523","article-title":"The role of Stat5a and Stat5b in signaling by IL-2 family cytokines","volume":"19","author":"Lin","year":"2000","journal-title":"Oncogene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/j.1471-4159.2007.05099.x","article-title":"Role of ATP-binding cassette transporters in brain lipid transport and neurological disease","volume":"104","author":"Kim","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Dib, S., Pahnke, J., and Gosselet, F. (2021). Role of ABCA7 in Human Health and in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094603"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1161\/01.ATV.0000235720.61091.c7","article-title":"HSPA12B is predominantly expressed in endothelial cells and required for angiogenesis","volume":"26","author":"Steagall","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Przybylowicz, P.K., Klepinowski, T., Taryma-Le\u015bniak, O., Bi\u0144kowski, J., and Wojdacz, T.K. (2025). Evaluation of methylation changes in blood cells of COVID-19 patients as a biomarker of severity of the infection. BMC Infect. Dis., 25.","DOI":"10.1186\/s12879-025-11181-1"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Balnis, J., Madrid, A., Drake, L.A., Vancavage, R., Tiwari, A., Patel, V.J., Ramos, R.B., Schwarz, J.J., Yucel, R., and Singer, H.A. (2024). Blood DNA methylation in post-acute sequelae of COVID-19 (PASC): A prospective cohort study. EBioMedicine, 106.","DOI":"10.1016\/j.ebiom.2024.105251"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Granvik, C., Persson, I.-L., Barros, G.W.F., Ahlm, C., Forsell, M.N.E., Tevell, S., Sundh, J., Blomberg, A., Lind, A., and Cajander, S. (2025). Long-Term Physical Capacity Following COVID-19: A Prospective, Three-Year Study. medRxiv.","DOI":"10.2139\/ssrn.5247989"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Pagliaro, P., and Penna, C. (2020). ACE\/ACE2 Ratio: A Key Also in 2019 Coronavirus Disease (Covid-19)?. Front. Med., 7.","DOI":"10.3389\/fmed.2020.00335"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1300\/J092v11n01_02","article-title":"Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"11","author":"Carruthers","year":"2003","journal-title":"J. Chronic Fatigue Syndr."},{"key":"ref_58","unstructured":"WHO (2021, October 06). A Clinical Case Definition of Post COVID-19 Condition by a Delphi Consensus. Available online: https:\/\/www.who.int\/publications\/i\/item\/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-1-0716-4498-0_9","article-title":"Application of DNA Methylome Analysis to Patients with ME\/CFS","volume":"2920","author":"Peppercorn","year":"2025","journal-title":"Methods Mol. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ludgate, J.L., Wright, J., Stockwell, P.A., Morison, I.M., Eccles, M.R., and Chatterjee, A. (2017). A streamlined method for analysing genome-wide DNA methylation patterns from low amounts of FFPE DNA. BMC Med. Genomics, 10.","DOI":"10.1186\/s12920-017-0290-1"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"102714","DOI":"10.1016\/j.xpro.2023.102714","article-title":"Protocol for generating high-quality genome-scale DNA methylation sequencing data from human cancer biospecimens","volume":"4","author":"Rodger","year":"2023","journal-title":"STAR Protoc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1093\/bioinformatics\/btu126","article-title":"DMAP: Differential methylation analysis package for RRBS and WGBS data","volume":"30","author":"Stockwell","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e79","DOI":"10.1093\/nar\/gks150","article-title":"Comparison of alignment software for genome-wide bisulphite sequence data","volume":"40","author":"Chatterjee","year":"2012","journal-title":"Nucleic. Acids. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6631\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:08:01Z","timestamp":1760033281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6631"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":63,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26146631"],"URL":"https:\/\/doi.org\/10.3390\/ijms26146631","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]}}}