Clinical Epigenetics最新文献

{"title":"Methylome-wide association analyses of lipids and modifying effects of behavioral factors in diverse race and ethnicity participants.","authors":"Yao Hu, Jeff Haessler, Jessica I Lundin, Burcu F Darst, Eric A Whitsel, Megan Grove, Weihua Guan, Rui Xia, Mindy Szeto, Laura M Raffield, Scott Ratliff, Yuxuan Wang, Xuzhi Wang, Alison E Fohner, Megan T Lynch, Yesha M Patel, S Lani Park, Huichun Xu, Braxton D Mitchell, Joshua C Bis, Nona Sotoodehnia, Jennifer A Brody, Bruce M Psaty, Gina M Peloso, Michael Y Tsai, Stephen S Rich, Jerome I Rotter, Jennifer A Smith, Sharon L R Kardia, Alex P Reiner, Leslie Lange, Myriam Fornage, James S Pankow, Mariaelisa Graff, Kari E North, Charles Kooperberg, Ulrike Peters","doi":"10.1186/s13148-025-01859-3","DOIUrl":"https://doi.org/10.1186/s13148-025-01859-3","url":null,"abstract":"<p><p>Circulating lipid concentrations are clinically associated with cardiometabolic diseases. The phenotypic variance explained by identified genetic variants remains limited, highlighting the importance of searching for additional factors beyond genetic sequence variants. DNA methylation has been linked to lipid concentrations in previous studies, although most of the studies harbored moderate sample sizes and exhibited underrepresentation of non-European ancestry populations. In addition, knowledge of nongenetic factors on lipid profiles is extremely limited. In the Population Architecture Using Genomics and Epidemiology (PAGE) Study, we performed methylome-wide association analysis on 9,561 participants from diverse race and ethnicity backgrounds for HDL-c, LDL-c, TC, and TG levels, and also tested interactions between smoking or alcohol intake and methylation in their association with lipid levels. We identified novel CpG sites at 16 loci (P < 1.18E-7) with successful replication on 3,215 participants. One additional novel locus was identified in the self-reported White participants (P = 4.66E-8). Although no additional CpG sites were identified in the genome-wide interaction analysis, 13 reported CpG sites showed significant heterogeneous association across smoking or alcohol intake strata. By mapping novel and reported CpG sites to genes, we identified enriched pathways directly linked to lipid metabolism as well as ones spanning various biological functions. These findings provide new insights into the regulation of lipid concentrations.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"54"},"PeriodicalIF":4.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep disturbances, shift work, and epigenetic ageing in working-age adults: findings from the Young Finns study.","authors":"Ida Autio, Aino Saarinen, Saara Marttila, Emma Raitoharju, Pashupati P Mishra, Nina Mononen, Mika Kähönen, Liisa Keltikangas-Järvinen, Olli Raitakari, Terho Lehtimäki","doi":"10.1186/s13148-025-01860-w","DOIUrl":"https://doi.org/10.1186/s13148-025-01860-w","url":null,"abstract":"<p><strong>Background: </strong>Sleep disturbances are known to have adverse effects on health, but knowledge on the effect of sleep disturbances on epigenetic ageing is limited. We investigated (1) whether symptoms of insomnia, obstructive sleep apnoea, sleep deprivation, and circadian rhythm lateness are associated with epigenetic ageing, and (2) whether years spent in shift work moderates these associations.</p><p><strong>Methods: </strong>We used the population-based Young Finns data (n = 1618). Epigenetic clocks such as AgeDev_Hannum, AgeDev_Horvath, AgeDev_Pheno, AgeDev_Grim, and DunedinPACE were utilized to measure epigenetic ageing. Sleep was evaluated using various validated self-report questionnaires. Covariates included sex, array type, smoking status, health behaviours, socioeconomic factors, and cardiovascular health factors.</p><p><strong>Results: </strong>Among the various sleep measures, obstructive sleep apnoea symptoms were most consistently linked to accelerated epigenetic ageing, as measured by AgeDev_Grim and DunedinPACE. Insomnia, sleep deprivation, and years spent in shift work were not associated with epigenetic ageing after adjusting for health-related or socioeconomic covariates. Additionally, we found interactions between years spent in shift work and sleep disturbances when accounting for epigenetic ageing. Among those with little to no history of shift work, both insomnia and sleep deprivation were associated with more accelerated epigenetic ageing in AgeDev_Grim when compared to long-term shift workers. However, the pace of epigenetic ageing (measured with DunedinPACE) appears to be higher in those with both sleep deprivation and longer history of shift work.</p><p><strong>Conclusions: </strong>Among various sleep measures, symptoms of obstructive sleep apnoea appear to be most consistently associated with accelerated epigenetic ageing even after adjusting for various health-related and socioeconomic factors. Shift work seems to have a crucial role in the relationship between sleep disturbances and epigenetic ageing in working-age adults.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"55"},"PeriodicalIF":4.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Respiratory infection‑ and asthma‑prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways.","authors":"David Martino, Nikki Schultz, Ravinder Kaur, Simon D van Haren, Nina Kresoje, Annmarie Hoch, Joann Diray-Arce, Jessica Lasky Su, Ofer Levy, Michael Pichichero","doi":"10.1186/s13148-025-01848-6","DOIUrl":"https://doi.org/10.1186/s13148-025-01848-6","url":null,"abstract":"","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"53"},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of 1,25(OH)₂D₃ on Dickkopf-1 methylation in colorectal cancer.","authors":"Hongyan Sun, Liehao Yang, Nan Li, Yue Hu, Qianying Hu, Zilong Zhou, Xianling Cong","doi":"10.1186/s13148-025-01857-5","DOIUrl":"10.1186/s13148-025-01857-5","url":null,"abstract":"<p><strong>Background: </strong>Vitamin D is a fat-soluble vitamin that has a protective role in colorectal cancer. Several studies have identified the association between vitamin D and changes in DNA methylation in different types of tumours. Dickkopf-1 (DKK1) inhibits the Wnt/β-catenin signalling pathway, and 1,25(OH)₂D₃ can induce DKK1 expression in colorectal cancer. However, whether 1,25(OH)₂D₃ can affect DKK1 expression by regulating DNA methylation in colorectal cancer is not known.</p><p><strong>Methods: </strong>Fifty-seven colorectal cancer (CRC) patients and fifty-five healthy controls were included in this study. Serum DKK1 and 25(OH)D levels were measured via ELISA and liquid chromatography‒tandem mass spectrometry, respectively, and the associations of DKK1 with clinicopathological characteristics and 25(OH)D were analysed. A DKK1 expression plasmid was transfected into cells to assess the functional significance of DKK1 in CRC progression via CCK8, wound healing and migration assays. BiSulphite Amplicon Sequencing (BSAS) and methylation-specific PCR were used to detect the DKK1 methylation status of colorectal cancer cells and tissues. The effect of 1,25(OH)₂D₃ on DKK1 methylation was investigated by pyrosequencing. A dual-luciferase reporter assay was performed to investigate the influence of CpG island methylation on DKK1 transcriptional activity.</p><p><strong>Results: </strong>A decreased serum DKK1 level was closely associated with nerve infiltration and 25(OH)D status in patients with colorectal cancer. Overexpression of DKK1 reduced the proliferative and migratory capabilities of colorectal cancer cells. The methylation patterns of DKK1 (- 195 to + 231), including 31 CpG sites, were assayed via BSAS in CRC cells and tissues. Compared with those in adjacent normal tissues, the methylation levels of multiple CpG sites located in the promoter, 5'UTR and exon 1 were increased in tumour tissues. DKK1 hypermethylation was associated with decreased DKK1 expression in colorectal cancer cells and tissues. 1,25(OH)₂D₃ induced DKK1 expression in colorectal cancer cells, and pyrosequencing revealed that 1,25(OH)₂D₃ treatment induced demethylation of CpG sites located in the promoter (- 97 to - 32) and 5'UTR (+ 39 to + 97). The dual-luciferase reporter assay further confirmed that CpG island methylation (-120 to + 225) directly represses DKK1 transcription.</p><p><strong>Conclusion: </strong>DKK1 functions as a tumour suppressor in colorectal cancer, and 1,25(OH)₂D₃ upregulates DKK1 expression by inducing demethylation of the DKK1 promoter and 5'UTR in specific colorectal cancer cell lines.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"52"},"PeriodicalIF":4.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic regulators combined with tumour immunotherapy: current status and perspectives.","authors":"Huan Zhang, Yutong Pang, Ling Yi, Xiaojue Wang, Panjian Wei, Haichao Wang, Shuye Lin","doi":"10.1186/s13148-025-01856-6","DOIUrl":"10.1186/s13148-025-01856-6","url":null,"abstract":"<p><p>Immunotherapy, particularly immune checkpoint inhibitor therapy, has demonstrated clinical benefits in solid tumours. Despite its satisfactory clinical efficacy, it still faces several issues, such as limited eligibility, low response rates and cytotoxicity. Cancer epigenetics implies that tumour cells exhibit unique phenotypes because of their unique characteristics, thus reprogramming of the epigenome holds promise for cancer therapy. Epigenetic regulation plays an important role in regulating gene expression during tumour development and maintenance. Epigenetic regulators induce cancer cell cycle arrest, apoptosis and differentiation of cancer cells, thereby exerting anti-tumour effects. Recent studies have revealed a significant correlation between epigenetic regulatory factors and immune checkpoint therapy. Epigenetics can modulate various aspects of the tumour immune microenvironment and immune response to enhance the sensitivity of immunotherapy, such as lowering the concentration required and mitigating cytotoxicity. This review primarily discusses DNA methyltransferase inhibitors, histone deacetylase inhibitors, enhancer of zeste homolog 2 inhibitors and lysine-specific demethylase 1 inhibitors, which are associated with transcriptional repression. This repression alters the expression of genes involved in the immune checkpoint, thereby enhancing the effectiveness of immunotherapy. We also discuss the potential and challenges of tumour immunotherapy and highlight its advantages, application challenges and clinical research on integrating epigenetic regulatory factors with tumour immunotherapy.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"51"},"PeriodicalIF":4.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation heterogeneity correlates with field cancerization and prognosis in lung adenocarcinoma patients.","authors":"Ying Zhou, Jing Zhang, Yang He, Yun Wang, Bing Li, Tengfei Zhu, Yanjun Su","doi":"10.1186/s13148-025-01845-9","DOIUrl":"10.1186/s13148-025-01845-9","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. The distinctive genetic and epigenetic modifications in tumors and paired non-malignant samples, such as adjacent peri-tumor and tumor-distant normal lung tissues, have not been adequately studied.</p><p><strong>Methods: </strong>We recruited 57 patients with resectable stage I-III LUAD and collected matched samples of the primary tumor, peri-tumoral tissues, and tumor-distant normal lung tissue. We performed bisulfite sequencing using a custom methylation panel to profile DNA methylation levels and obtained somatic variation landscape through targeted next-generation sequencing (NGS). We attempted to identify differential methylation blocks (DMBs) between the tumor, peri-tumor, and normal tissues.</p><p><strong>Results: </strong>We analyzed the DNA methylation patterns of matched tumor, peri-tumor, and normal lung tissue samples from 57 LUAD patients. No significantly different methylation blocks were found between peri-tumoral and normal tissues, while they both exhibited distinct methylation profiles compared to tumor tissues. A total of 1329 tumor-specific DMBs, which are potentially associated with aberrant gene expression in LUAD, were identified. Utilizing a consensus clustering algorithm, we classified the tumor samples into two subgroups (C1 and C2) based on distinct methylation profiles, independent of the patient's sex, tumor stage, smoking history, and tumor cell fraction. The C2 subgroup exhibited a higher malignancy density ratio (MD ratio), suggesting a more pronounced degree of field cancerization, while the C1 subgroup was characterized by a higher frequency of EGFR mutations. The DMBs between the two subgroups were enriched in the calcium signaling pathway. Notably, P2RX2 shows significant hypermethylation in the C2 subgroup, and its low expression in the external The Cancer Genome Atlas (TCGA) cohort may correlate with reduced overall survival in LUAD patients.</p><p><strong>Conclusion: </strong>Our findings revealed distinct methylation patterns between tumor and pre-malignant samples, such as peri-tumor and normal tissues. Moreover, our study suggests that distinct clustering based on DNA methylation may indicate different prognoses in LUAD patients.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"50"},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 diabetes impacts DNA methylation in human sperm.","authors":"Lei Su, Jonathan M Dreyfuss, Rafael Ferraz Bannitz, Danielle Wolfs, Georgia Hansbury, Lauren Richardson, Charnice Charmant, Jay Patel, Elizabeth S Ginsburg, Catherine Racowsky, Ruby Fore, Vissarion Efthymiou, Jessica Desmond, Allison Goldfine, Anne Ferguson-Smith, Hui Pan, Marie-France Hivert, Elvira Isganaitis, Mary Elizabeth Patti","doi":"10.1186/s13148-025-01853-9","DOIUrl":"10.1186/s13148-025-01853-9","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Disorders of the reproductive system, including hypogonadism and reduced fertility, are an under-recognized complication of diabetes. Based on experimental data in mice, hyperglycemia and obesity may modify epigenetic marks in sperm and impact health and development of offspring, but data are more limited in humans. Thus, we sought to study the impact of type 2 diabetes and glycemic control on sperm quality and DNA methylation.</p><p><strong>Methods: </strong>In this prospective cohort study, we recruited 40 men with BMI greater than 25 kg/m² including 18 with type 2 diabetes, 6 with prediabetes, and 16 normoglycemic controls. Assessments were repeated after 3 months in 9 men with type 2 diabetes and 7 controls. We analyzed reproductive hormones, sperm concentration and motility, and sperm DNA methylation (MethylationEPIC BeadChip).</p><p><strong>Results: </strong>Men with type 2 diabetes had higher levels of follicle-stimulating hormone (FSH), but similar testosterone levels and sperm quality as controls. Sperm DNA methylation was stable with repeat sampling at 3 months in men with and without type 2 diabetes. We identified differential methylation at 655 of 745,804 CpG sites in men with type 2 diabetes versus controls (FDR < 0.05). Of these, 96.5% showed higher methylation in type 2 diabetes, with a mean difference in DNA methylation (beta value, β) of 0.16 ± 0.004 (16 ± 0.4%). Ontology analysis of differentially methylated loci revealed annotation to genes regulating synaptic signaling, actin, cAMP-dependent pathways, and G protein-coupled receptor pathways. 24% of probes differentially regulated in men with type 2 diabetes versus control overlapped with probes associated with HbA1c, suggesting additional factors beyond glycemic control contributed to diabetes-associated differences in DNA methylation.</p><p><strong>Conclusions/interpretation: </strong>Men with type 2 diabetes showed higher DNA methylation levels in sperm relative to normoglycemic controls with similar BMI. Whether these differences are reversible with glucose-lowering treatment or may contribute to post-fertilization transcriptional regulation warrants further investigation.</p><p><strong>Trial registration: </strong>NCT03860558.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"49"},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic regulatory protein chromobox family regulates multiple signalling pathways and mechanisms in cancer.","authors":"Weiyu Su, Weiwen Wang, Guanghui Zhang, Lianhe Yang","doi":"10.1186/s13148-025-01852-w","DOIUrl":"10.1186/s13148-025-01852-w","url":null,"abstract":"<p><p>Signal transduction plays a pivotal role in modulating a myriad of critical processes, including the tumour microenvironment (TME), cell cycle arrest, proliferation and apoptosis of tumour cells, as well as their migration, invasion, and the epithelial-mesenchymal transition (EMT). Epigenetic mechanisms are instrumental in the genesis and progression of tumours. The Chromobox (CBX) family proteins, which serve as significant epigenetic regulators, exhibit tumour-specific expression patterns and biological functionalities. These proteins are influenced by a multitude of factors and could modulate the activation of diverse signalling pathways within tumour cells through alterations in epigenetic modifications, thereby acting as either oncogenic agents or tumour suppressors. This review aims to succinctly delineate the composition, structure, function, and expression of CBXs within tumour cells, with an emphasis on synthesizing and deliberating the CBXs-mediated activation of intracellular signalling pathways and the intricate mechanisms governing tumourigenesis and progression. Moreover, a plethora of contemporary studies have substantiated that CBXs might represent a promising target for the diagnosis and therapeutic intervention of tumour patients. We have also compiled and scrutinized the current research landscape concerning inhibitors targeting CBXs, aspiring to aid researchers in gaining a deeper comprehension of the biological roles and mechanisms of CBXs in the malignant evolution of tumours, and to furnish novel perspectives for the innovation of targeted tumour therapeutics.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"48"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNUH methylation classifier for CNS tumors.","authors":"Kwanghoon Lee, Jaemin Jeon, Jin Woo Park, Suwan Yu, Jae-Kyung Won, Kwangsoo Kim, Chul-Kee Park, Sung-Hye Park","doi":"10.1186/s13148-025-01824-0","DOIUrl":"10.1186/s13148-025-01824-0","url":null,"abstract":"<p><strong>Background: </strong>Methylation profiling of central nervous system (CNS) tumors, pioneered by the German Cancer Research Center, has significantly improved diagnostic accuracy. This study aimed to further enhance the performance of methylation classifiers by leveraging publicly available data and innovative machine-learning techniques.</p><p><strong>Results: </strong>Seoul National University Hospital Methylation Classifier (SNUH-MC) addressed data imbalance using the Synthetic Minority Over-sampling Technique (SMOTE) algorithm and incorporated OpenMax within a Multi-Layer Perceptron to prevent labeling errors in low-confidence diagnoses. Compared to two published CNS tumor methylation classification models (DKFZ-MC: Deutsches Krebsforschungszentrum Methylation Classifier v11b4: RandomForest, 767-MC: Multi-Layer Perceptron), our SNUH-MC showed improved performance in F1-score. For 'Filtered Test Data Set 1,' the SNUH-MC achieved higher F1-micro (0.932) and F1-macro (0.919) scores compared to DKFZ-MC v11b4 (F1-micro: 0.907, F1-macro: 0.627). We evaluated the performance of three classifiers; SNUH-MC, DKFZ-MC v11b4, and DKFZ-MC v12.5, using specific criteria. We set established 'Decisions' categories based on histopathology, clinical information, and next-generation sequencing to assess the classification results. When applied to 193 unknown SNUH methylation data samples, SNUH-MC notably improved diagnosis compared to DKFZ-MC v11b4. Specifically, 17 cases were reclassified as 'Match' and 34 cases as 'Likely Match' when transitioning from DKFZ-MC v11b4 to SNUH-MC. Additionally, SNUH-MC demonstrated similar results to DKFZ-MC v12.5 for 23 cases that were unclassified by v11b4.</p><p><strong>Conclusions: </strong>This study presents SNUH-MC, an innovative methylation-based classification tool that significantly advances the field of neuropathology and bioinformatics. Our classifier incorporates cutting-edge techniques such as the SMOTE and OpenMax resulting in improved diagnostic accuracy and robustness, particularly when dealing with unknown or noisy data.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"47"},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenome-wide association study for dilated cardiomyopathy in left ventricular heart tissue identifies putative gene sets associated with cardiac pathology and early indicators of cardiac risk.","authors":"Konstanze Tan, Darwin Tay, Wilson Tan, Hong Kiat Ng, Eleanor Wong, Michael P Morley, Gurpreet K Singhera, Chang Jie Mick Lee, Pritesh R Jain, Fei Li Tai, Paul J Hanson, Thomas P Cappola, Kenneth B Margulies, Roger Foo, Marie Loh","doi":"10.1186/s13148-025-01854-8","DOIUrl":"10.1186/s13148-025-01854-8","url":null,"abstract":"<p><strong>Background: </strong>Methylation changes linked to dilated cardiomyopathy (DCM) affect cardiac gene expression. We investigate DCM mechanisms regulated by CpG methylation using multi-omics and causal analyses in the largest cohort of left ventricular tissues available.</p><p><strong>Methods: </strong>We mapped DNA methylation at ~ 850,000 CpG sites, performed array-based genotyping and conducted RNA sequencing on left ventricular tissue samples from failing and non-failing hearts across two independent DCM cohorts (discovery n = 329, replication n = 85). Summary-data-based Mendelian Randomisation (SMR) was applied to explore the causal contribution of sentinel CpGs to DCM. Fine-mapping of regions surrounding sentinel CpGs revealed additional signals for cardiovascular disease risk factors. Coordinated changes across multiple CpG sites were examined using weighted gene co-expression network analysis (WGCNA).</p><p><strong>Results: </strong>We identified 194 epigenome-wide significant CpGs associated with DCM (discovery P < 5.96E-08), enriched in active chromatin states in heart tissue. Amongst these, 32 sentinel CpGs significantly influenced the expression of 30 unique proximal genes (± 1 Mb). SMR suggested the causal contribution of two sentinel CpGs to DCM and two other sentinel CpGs to the expression of two unique proximal genes (P < 0.05). For one sentinel CpG, colocalisation analyses provided suggestive evidence for a single causal variant underlying the methylation-gene expression relationship. Fine-mapping revealed additional signals linked to cardiovascular disease-relevant traits, including creatinine levels and the Framingham Risk Score. Co-methylation modules were enriched in gene sets and transcriptional regulators related to cardiac physiological and pathological processes, as well as in transcriptional regulators whose cardiac relevance has yet to be determined.</p><p><strong>Conclusions: </strong>Using the largest series of left ventricular tissue to date, this study investigates the causal role of cardiac methylation changes in DCM and suggests targets for experimental studies to probe DCM pathogenesis.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"45"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}