{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:50:14Z","timestamp":1793764214388,"version":"4.6.1"},"reference-count":93,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T00:00:00Z","timestamp":1744416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013428","name":"Muscles for Muscles","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"publisher","award":["184.034.019"],"award-info":[{"award-number":["184.034.019"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004243","name":"Princess Beatrix Foundation for Neuromuscular Diseases","doi-asserted-by":"publisher","award":["W.OB21-01"],"award-info":[{"award-number":["W.OB21-01"]}],"id":[{"id":"10.13039\/501100004243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010665","name":"EU Framework Programme for Research and Innovation Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["956185"],"award-info":[{"award-number":["956185"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["772376 - EScORIAL"],"award-info":[{"award-number":["772376 - EScORIAL"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2025,5]]},"DOI":"10.1016\/j.isci.2025.112461","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T19:44:47Z","timestamp":1744919087000},"page":"112461","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"title":["Comprehensive analysis across SMN2 excludes DNA methylation as an epigenetic biomarker for spinal muscular atrophy"],"prefix":"10.1016","volume":"28","author":[{"given":"Maria M.","family":"Zwartkruis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris V.","family":"Kortooms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demi","family":"Gommers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin G.","family":"Elferink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Signoria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"van der Sel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Hop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona A.J.","family":"Zwamborn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Geene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared W.","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanneke W.M.","family":"van Deutekom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"van Rheenen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H.","family":"Veldink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fay-Lynn","family":"Asselman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renske I.","family":"Wadman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Ludo","family":"van der Pol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijs W.","family":"van Haaften","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2330-9444","authenticated-orcid":false,"given":"Ewout J.N.","family":"Groen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2025.112461_bib1","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13023-017-0671-8","article-title":"Prevalence, incidence and carrier frequency of 5q\u2013linked spinal muscular atrophy \u2013 a literature review","volume":"12","author":"Verhaart","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"10.1016\/j.isci.2025.112461_bib2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"10.1016\/j.isci.2025.112461_bib3","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/ng0797-265","article-title":"Correlation between severity and SMN protein level in spinal muscular atrophy","volume":"16","author":"Lefebvre","year":"1997","journal-title":"Nat. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib4","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","article-title":"A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy","volume":"96","author":"Lorson","year":"1999","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.isci.2025.112461_bib5","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1093\/hmg\/8.7.1177","article-title":"A Single Nucleotide Difference That Alters Splicing Patterns Distinguishes the SMA Gene SMN1 From the Copy Gene SMN2","volume":"8","author":"Monani","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib6","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.nmd.2018.01.003","article-title":"Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases","volume":"28","author":"Calucho","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"10.1016\/j.isci.2025.112461_bib7","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.tins.2020.11.009","article-title":"Spinal Muscular Atrophy: In the Challenge Lies a Solution","volume":"44","author":"Wirth","year":"2021","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.isci.2025.112461_bib8","doi-asserted-by":"crossref","DOI":"10.1093\/braincomms\/fcaa075","article-title":"Intragenic and structural variation in the SMN locus and clinical variability in spinal muscular atrophy","volume":"2","author":"Wadman","year":"2020","journal-title":"Brain Commun."},{"key":"10.1016\/j.isci.2025.112461_bib9","doi-asserted-by":"crossref","first-page":"4817","DOI":"10.1172\/JCI124120","article-title":"Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment","volume":"129","author":"Ramos","year":"2019","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.isci.2025.112461_bib10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0167087","article-title":"A Comparative Study of SMN Protein and mRNA in Blood and Fibroblasts in Patients with Spinal Muscular Atrophy and Healthy Controls","volume":"11","author":"Wadman","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.isci.2025.112461_bib11","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41572-022-00380-8","article-title":"Spinal muscular atrophy","volume":"8","author":"Mercuri","year":"2022","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.isci.2025.112461_bib12","doi-asserted-by":"crossref","first-page":"fcac269","DOI":"10.1093\/braincomms\/fcac269","article-title":"Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study","volume":"4","author":"Scheijmans","year":"2022","journal-title":"Brain Commun."},{"key":"10.1016\/j.isci.2025.112461_bib13","doi-asserted-by":"crossref","first-page":"9029","DOI":"10.3390\/ijms22169029","article-title":"The Importance of Digging into the Genetics of SMN Genes in the Therapeutic Scenario of Spinal Muscular Atrophy","volume":"22","author":"Costa-Roger","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.isci.2025.112461_bib14","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.neuron.2016.11.033","article-title":"The Antisense Transcript SMN-AS1 Regulates SMN Expression and Is a Novel Therapeutic Target for Spinal Muscular Atrophy","volume":"93","author":"d\u2019Ydewalle","year":"2017","journal-title":"Neuron"},{"key":"10.1016\/j.isci.2025.112461_bib15","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/acn3.689","article-title":"Novel challenges in spinal muscular atrophy \u2013 How to screen and whom to treat?","volume":"6","author":"Saffari","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"10.1016\/j.isci.2025.112461_bib16","article-title":"Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine","volume":"2","author":"Chaytow","year":"2021","journal-title":"Cell Rep. Med."},{"key":"10.1016\/j.isci.2025.112461_bib17","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41580-019-0159-6","article-title":"The diverse roles of DNA methylation in mammalian development and disease","volume":"20","author":"Greenberg","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.isci.2025.112461_bib18","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/hmg\/ddn357","article-title":"Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition","volume":"18","author":"Hauke","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib19","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1631\/jzus.B1500072","article-title":"Association between SMN2 methylation and disease severity in Chinese children with spinal muscular atrophy","volume":"17","author":"Cao","year":"2016","journal-title":"J. Zhejiang Univ. - Sci. B"},{"key":"10.1016\/j.isci.2025.112461_bib20","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1093\/hmg\/ddab350","article-title":"Antisense oligonucleotides targeting the SMN2 promoter region enhance SMN2 expression in spinal muscular atrophy cell lines and mouse model","volume":"31","author":"Wang","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib21","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/ejhg.2012.293","article-title":"Genome-wide analysis shows association of epigenetic changes in regulators of Rab and Rho GTPases with spinal muscular atrophy severity","volume":"21","author":"Zheleznyakova","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0121964","article-title":"Methylation Levels of SLC23A2 and NCOR2 Genes Correlate with Spinal Muscular Atrophy Severity","volume":"10","author":"Zheleznyakova","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.isci.2025.112461_bib23","first-page":"25","article-title":"Long-read sequencing identifies copy-specific markers of SMN gene conversion in spinal muscular atrophy","volume":"17","author":"Zwartkruis","year":"2024","journal-title":"Genome Med."},{"key":"10.1016\/j.isci.2025.112461_bib24","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41586-022-05580-6","article-title":"A DNA methylation atlas of normal human cell types","volume":"613","author":"Loyfer","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.isci.2025.112461_bib25","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.ajhg.2023.01.001","article-title":"Comprehensive SMN1 and SMN2 profiling for spinal muscular atrophy analysis using long-read PacBio HiFi sequencing","volume":"110","author":"Chen","year":"2023","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib26","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1080\/15592294.2021.1950990","article-title":"Human non-CpG methylation patterns display both tissue-specific and inter-individual differences suggestive of underlying function","volume":"17","author":"Titcombe","year":"2022","journal-title":"Epigenetics"},{"key":"10.1016\/j.isci.2025.112461_bib27","doi-asserted-by":"crossref","first-page":"823","DOI":"10.4161\/epi.28741","article-title":"The evidence for functional non-CpG methylation in mammalian cells","volume":"9","author":"Patil","year":"2014","journal-title":"Epigenetics"},{"key":"10.1016\/j.isci.2025.112461_bib28","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/nature10442","article-title":"CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing","volume":"479","author":"Shukla","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.isci.2025.112461_bib29","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrg3663","article-title":"CTCF: an architectural protein bridging genome topology and function","volume":"15","author":"Ong","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib30","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41594-024-01241-6","article-title":"The impact of DNA methylation on CTCF-mediated 3D genome organization","volume":"31","author":"Monteagudo-S\u00e1nchez","year":"2024","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.isci.2025.112461_bib31","doi-asserted-by":"crossref","first-page":"D252","DOI":"10.1093\/nar\/gkx1106","article-title":"HOCOMOCO: towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis","volume":"46","author":"Kulakovskiy","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2025.112461_bib32","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/bioinformatics\/btr064","article-title":"FIMO: scanning for occurrences of a given motif","volume":"27","author":"Grant","year":"2011","journal-title":"Bioinformatics"},{"key":"10.1016\/j.isci.2025.112461_bib33","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.nmd.2007.05.009","article-title":"An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients","volume":"17","author":"O\u2019Hagen","year":"2007","journal-title":"Neuromuscul. Disord."},{"key":"10.1016\/j.isci.2025.112461_bib34","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.ajhg.2009.08.002","article-title":"A Positive Modifier of Spinal Muscular Atrophy in the SMN2 Gene","volume":"85","author":"Prior","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib35","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1093\/hmg\/ddx166","article-title":"A-44G transition in SMN2 intron 6 protects patients with spinal muscular atrophy","volume":"26","author":"Wu","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib36","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1016\/j.cell.2022.04.031","article-title":"Counteracting chromatin effects of a splicing-correcting antisense oligonucleotide improves its therapeutic efficacy in spinal muscular atrophy","volume":"185","author":"Marasco","year":"2022","journal-title":"Cell"},{"key":"10.1016\/j.isci.2025.112461_bib37","article-title":"DNA methylation subpatterns at distinct regulatory regions in human early embryos","volume":"8","author":"Luo","year":"2018","journal-title":"Open Biol."},{"key":"10.1016\/j.isci.2025.112461_bib38","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ebiom.2019.04.045","article-title":"Pan-cancer genomic analysis links 3\u2019UTR DNA methylation with increased gene expression in T cells","volume":"43","author":"McGuire","year":"2019","journal-title":"EBioMedicine"},{"key":"10.1016\/j.isci.2025.112461_bib39","doi-asserted-by":"crossref","first-page":"569","DOI":"10.2217\/epi-2022-0098","article-title":"FAM81A Identified as a Stemness-Related Gene by Screening DNA Methylation Sites Based on Machine Learning-Accessed Stemness in Pancreatic Cancer","volume":"14","author":"Zhang","year":"2022","journal-title":"Epigenomics"},{"key":"10.1016\/j.isci.2025.112461_bib40","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/sj.onc.1202299","article-title":"Hypermethylation of the cell cycle inhibitor p15INK4b 3\u2032-untranslated region interferes with its transcriptional regulation in primary lymphomas","volume":"18","author":"Malumbres","year":"1999","journal-title":"Oncogene"},{"key":"10.1016\/j.isci.2025.112461_bib41","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.4161\/epi.29068","article-title":"Functional DNA methylation in a transcript specific 3\u2032UTR region of TrkB associates with suicide","volume":"9","author":"Maussion","year":"2014","journal-title":"Epigenetics"},{"key":"10.1016\/j.isci.2025.112461_bib42","doi-asserted-by":"crossref","first-page":"81571","DOI":"10.18632\/oncotarget.13147","article-title":"Epigenetic upregulation of ARL4C, due to DNA hypomethylation in the 3\u2019-untranslated region, promotes tumorigenesis of lung squamous cell carcinoma","volume":"7","author":"Fujii","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.isci.2025.112461_bib43","first-page":"2137","article-title":"Overexpression of BHLHE41, correlated with DNA hypomethylation in 3\u2019UTR region, promotes the growth of human clear cell renal cell carcinoma","volume":"41","author":"Shen","year":"2019","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.isci.2025.112461_bib44","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/s42003-021-02621-0","article-title":"Age-related demethylation of the TDP-43 autoregulatory region in the human motor cortex","volume":"4","author":"Koike","year":"2021","journal-title":"Commun. Biol."},{"key":"10.1016\/j.isci.2025.112461_bib45","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/6019637","article-title":"Overexpression of eIF3D in Lung Adenocarcinoma Is a New Independent Prognostic Marker of Poor Survival","volume":"2019","author":"Wang","year":"2019","journal-title":"Dis. Markers"},{"key":"10.1016\/j.isci.2025.112461_bib46","doi-asserted-by":"crossref","first-page":"28990","DOI":"10.18632\/oncotarget.15993","article-title":"Genome-wide DNA methylation analysis reveals molecular subtypes of pancreatic cancer","volume":"8","author":"Mishra","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.isci.2025.112461_bib47","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13148-020-00876-8","article-title":"Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets","volume":"12","author":"Krushkal","year":"2020","journal-title":"Clin. Epigenetics"},{"key":"10.1016\/j.isci.2025.112461_bib48","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1093\/nar\/gkr1057","article-title":"Recognition of methylated DNA through methyl-CpG binding domain proteins","volume":"40","author":"Zou","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2025.112461_bib49","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.molcel.2020.03.024","article-title":"DNA Methylation Regulates Alternative Polyadenylation via CTCF and the Cohesin Complex","volume":"78","author":"Nanavaty","year":"2020","journal-title":"Mol. Cell"},{"key":"10.1016\/j.isci.2025.112461_bib50","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/s41580-022-00507-5","article-title":"Context-specific regulation and function of mRNA alternative polyadenylation","volume":"23","author":"Mitschka","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.isci.2025.112461_bib51","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13072-018-0205-1","article-title":"Consistent inverse correlation between DNA methylation of the first intron and gene expression across tissues and species","volume":"11","author":"Anastasiadi","year":"2018","journal-title":"Epigenetics Chromatin"},{"key":"10.1016\/j.isci.2025.112461_bib52","doi-asserted-by":"crossref","first-page":"R89","DOI":"10.1093\/hmg\/ddaa154","article-title":"Regulation, diversity and function of MECP2 exon and 3\u2032UTR isoforms","volume":"29","author":"Rodrigues","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib53","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.ccr.2014.07.028","article-title":"Gene Body Methylation Can Alter Gene Expression and Is a Therapeutic Target in Cancer","volume":"26","author":"Yang","year":"2014","journal-title":"Cancer Cell"},{"key":"10.1016\/j.isci.2025.112461_bib54","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41580-022-00483-w","article-title":"Establishment of H3K9-methylated heterochromatin and its functions in tissue differentiation and maintenance","volume":"23","author":"Padeken","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.isci.2025.112461_bib55","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41588-024-02038-5","article-title":"Profiling the epigenome using long-read sequencing","volume":"57","author":"Liu","year":"2025","journal-title":"Nat. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib56","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/s43587-023-00462-6","article-title":"Universal DNA methylation age across mammalian tissues","volume":"3","author":"Lu","year":"2023","journal-title":"Nat. Aging"},{"key":"10.1016\/j.isci.2025.112461_bib57","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtm.2024.101379","article-title":"Patient-specific responses to SMN2 splice-modifying treatments in spinal muscular atrophy fibroblasts","volume":"32","author":"Signoria","year":"2024","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.isci.2025.112461_bib58","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41392-024-02039-0","article-title":"Epigenetics-targeted drugs: current paradigms and future challenges","volume":"9","author":"Dai","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.isci.2025.112461_bib59","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nrg2540","article-title":"Linking DNA methylation and histone modification: patterns and paradigms","volume":"10","author":"Cedar","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib60","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41576-021-00416-x","article-title":"Interplay between chromatin marks in development and disease","volume":"23","author":"Janssen","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib61","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1093\/hmg\/ddi130","article-title":"The role of histone acetylation in SMN gene expression","volume":"14","author":"Kernochan","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib62","doi-asserted-by":"crossref","first-page":"5093","DOI":"10.2174\/13816128113199990356","article-title":"Histone acetylation as a potential therapeutic target in motor neuron degenerative diseases","volume":"19","author":"Garbes","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"10.1016\/j.isci.2025.112461_bib63","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1517\/13543784.2015.1038341","article-title":"Investigational therapies for the treatment of spinal muscular atrophy","volume":"24","author":"Kaczmarek","year":"2015","journal-title":"Expert Opin. Investig. Drugs"},{"key":"10.1016\/j.isci.2025.112461_bib64","first-page":"CD006282","article-title":"Drug treatment for spinal muscular atrophy types II and III","volume":"1","author":"Wadman","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.isci.2025.112461_bib65","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/hmg\/dds437","article-title":"VPA response in SMA is suppressed by the fatty acid translocase CD36","volume":"22","author":"Garbes","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib66","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/jnc.14935","article-title":"Combined treatment with the histone deacetylase inhibitor LBH589 and a splice-switch antisense oligonucleotide enhances SMN2 splicing and SMN expression in Spinal Muscular Atrophy cells","volume":"153","author":"Pagliarini","year":"2020","journal-title":"J. Neurochem."},{"key":"10.1016\/j.isci.2025.112461_bib67","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.neuint.2017.02.016","article-title":"Combination of valproic acid and morpholino splice-switching oligonucleotide produces improved outcomes in spinal muscular atrophy patient-derived fibroblasts","volume":"108","author":"Farrelly-Rosch","year":"2017","journal-title":"Neurochem. Int."},{"key":"10.1016\/j.isci.2025.112461_bib68","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/s41587-024-02320-1","article-title":"Epigenome editing technologies for discovery and medicine","volume":"42","author":"McCutcheon","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.isci.2025.112461_bib69","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1038\/nbt.3658","article-title":"Targeted DNA demethylation in vivo using dCas9\u2013peptide repeat and scFv\u2013TET1 catalytic domain fusions","volume":"34","author":"Morita","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.isci.2025.112461_bib70","doi-asserted-by":"crossref","first-page":"5615","DOI":"10.1093\/nar\/gkw159","article-title":"Repurposing the CRISPR-Cas9 system for targeted DNA methylation","volume":"44","author":"Vojta","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2025.112461_bib71","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41576-022-00569-3","article-title":"Molecular mechanisms of environmental exposures and human disease","volume":"24","author":"Wu","year":"2023","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.isci.2025.112461_bib72","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13059-018-1514-1","article-title":"Epigenetic prediction of complex traits and death","volume":"19","author":"McCartney","year":"2018","journal-title":"Genome Biol."},{"key":"10.1016\/j.isci.2025.112461_bib74","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"10.1016\/j.isci.2025.112461_bib76","author":"Elferink"},{"key":"10.1016\/j.isci.2025.112461_bib78","series-title":"Nf-Core\/Methylseq: Huggy Mollusc. Version 2.6.0","author":"Ewels","year":"2024"},{"key":"10.1016\/j.isci.2025.112461_bib79","series-title":"R: A Language and Environment for Statistical Computing","year":"2024"},{"key":"10.1016\/j.isci.2025.112461_bib80","author":"Kolde"},{"key":"10.1016\/j.isci.2025.112461_bib81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v025.i01","article-title":"FactoMineR: An R Package for Multivariate Analysis","volume":"25","author":"L\u00ea","year":"2008","journal-title":"J. Stat. Softw."},{"key":"10.1016\/j.isci.2025.112461_bib82","author":"Kassambara"},{"key":"10.1016\/j.isci.2025.112461_bib83","author":"Champely"},{"key":"10.1016\/j.isci.2025.112461_bib84","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"10.1016\/j.isci.2025.112461_bib85","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1101\/gr.849004","article-title":"WebLogo: A Sequence Logo Generator","volume":"14","author":"Crooks","year":"2004","journal-title":"Genome Res."},{"key":"10.1016\/j.isci.2025.112461_bib86","author":"Zwartkruis"},{"key":"10.1016\/j.isci.2025.112461_bib88","doi-asserted-by":"crossref","first-page":"e1634","DOI":"10.1212\/WNL.0000000000009248","article-title":"Population-based analysis of survival in spinal muscular atrophy","volume":"94","author":"Wijngaarde","year":"2020","journal-title":"Neurology"},{"key":"10.1016\/j.isci.2025.112461_bib89","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1056\/NEJMoa1710504","article-title":"Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy","volume":"378","author":"Mercuri","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.isci.2025.112461_bib90","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nmeth.3930","article-title":"Real-time selective sequencing using nanopore technology","volume":"13","author":"Loose","year":"2016","journal-title":"Nat. Methods"},{"key":"10.1016\/j.isci.2025.112461_bib91","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/s41587-020-00746-x","article-title":"Readfish enables targeted nanopore sequencing of gigabase-sized genomes","volume":"39","author":"Payne","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.isci.2025.112461_bib92","doi-asserted-by":"crossref","DOI":"10.1126\/science.abj6965","article-title":"Segmental duplications and their variation in a complete human genome","volume":"376","author":"Vollger","year":"2022","journal-title":"Science"},{"key":"10.1016\/j.isci.2025.112461_bib93","article-title":"Data files for: Segmental duplications and their variation in a complete human genome","author":"Vollger","year":"2021","journal-title":"Zenodo"},{"key":"10.1016\/j.isci.2025.112461_bib94","series-title":"Statistical Power Analysis for the Behavioral Sciences","author":"Cohen","year":"1988"},{"key":"10.1016\/j.isci.2025.112461_bib95","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abj0264","article-title":"Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS","volume":"14","author":"Hop","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.isci.2025.112461_bib96","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13073-019-0667-1","article-title":"Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing","volume":"11","author":"Zhang","year":"2019","journal-title":"Genome Med."},{"key":"10.1016\/j.isci.2025.112461_bib97","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13148-022-01279-7","article-title":"Characterising sex differences of autosomal DNA methylation in whole blood using the Illumina EPIC array","volume":"14","author":"Grant","year":"2022","journal-title":"Clin. Epigenetics"}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004225007229?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004225007229?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:40:49Z","timestamp":1776904849000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004225007229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":93,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["S2589004225007229"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2025.112461","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.11.21.24317551","asserted-by":"object"}]},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Comprehensive analysis across SMN2 excludes DNA methylation as an epigenetic biomarker for spinal muscular atrophy","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2025.112461","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"112461"}}