Epigenetics最新文献_第2页

Using methylation data to improve transcription factor binding prediction. 利用甲基化数据改进转录因子结合预测。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-02-01 DOI: 10.1080/15592294.2024.2309826

Daniel Morgan, Dawn L DeMeo, Kimberly Glass

{"title":"Using methylation data to improve transcription factor binding prediction.","authors":"Daniel Morgan, Dawn L DeMeo, Kimberly Glass","doi":"10.1080/15592294.2024.2309826","DOIUrl":"10.1080/15592294.2024.2309826","url":null,"abstract":"Modelling the regulatory mechanisms that determine cell fate, response to external perturbation, and disease state depends on measuring many factors, a task made more difficult by the plasticity of the epigenome. Scanning the genome for the sequence patterns defined by Position Weight Matrices (PWM) can be used to estimate transcription factor (TF) binding locations. However, this approach does not incorporate information regarding the epigenetic context necessary for TF binding. CpG methylation is an epigenetic mark influenced by environmental factors that is commonly assayed in human cohort studies. We developed a framework to score inferred TF binding locations using methylation data. We intersected motif locations identified using PWMs with methylation information captured in both whole-genome bisulfite sequencing and Illumina EPIC array data for six cell lines, scored motif locations based on these data, and compared with experimental data characterizing TF binding (ChIP-seq). We found that for most TFs, binding prediction improves using methylation-based scoring compared to standard PWM-scores. We also illustrate that our approach can be generalized to infer TF binding when methylation information is only proximally available, i.e. measured for nearby CpGs that do not directly overlap with a motif location. Overall, our approach provides a framework for inferring context-specific TF binding using methylation data. Importantly, the availability of DNA methylation data in existing patient populations provides an opportunity to use our approach to understand the impact of methylation on gene regulatory processes in the context of human disease.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2309826"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transmission of reduced levels of miR-34/449 from sperm to preimplantation embryos is a key step in the transgenerational epigenetic inheritance of the effects of paternal chronic social instability stress. miR-34/449水平的降低从精子传递到植入前胚胎是父代慢性社会不稳定压力影响的跨代表观遗传的关键步骤。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-05-13 DOI: 10.1080/15592294.2024.2346694

Alexandre Champroux, Yang Tang, David A Dickson, Alice Meng, Anne Harrington, Lucy Liaw, Matteo Marzi, Francesco Nicassio, Thorsten M Schlaeger, Larry A Feig

{"title":"Transmission of reduced levels of miR-34/449 from sperm to preimplantation embryos is a key step in the transgenerational epigenetic inheritance of the effects of paternal chronic social instability stress.","authors":"Alexandre Champroux, Yang Tang, David A Dickson, Alice Meng, Anne Harrington, Lucy Liaw, Matteo Marzi, Francesco Nicassio, Thorsten M Schlaeger, Larry A Feig","doi":"10.1080/15592294.2024.2346694","DOIUrl":"10.1080/15592294.2024.2346694","url":null,"abstract":"The transgenerational effects of exposing male mice to chronic social instability (CSI) stress are associated with decreased sperm levels of multiple members of the miR-34/449 family that persist after their mating through preimplantation embryo (PIE) development. Here we demonstrate the importance of these miRNA changes by showing that restoring miR-34c levels in PIEs derived from CSI stressed males prevents elevated anxiety and defective sociability normally found specifically in their adult female offspring. It also restores, at least partially, levels of sperm miR-34/449 normally reduced in their male offspring who transmit these sex-specific traits to their offspring. Strikingly, these experiments also revealed that inducing miR-34c levels in PIEs enhances the expression of its own gene and that of miR-449 in these cells. The same induction of embryo miR-34/449 gene expression likely occurs after sperm-derived miR-34c is introduced into oocytes upon fertilization. Thus, suppression of this miRNA amplification system when sperm miR-34c levels are reduced in CSI stressed mice can explain how a comparable fold-suppression of miR-34/449 levels can be found in PIEs derived from them, despite sperm containing ~50-fold lower levels of these miRNAs than those already present in PIEs. We previously found that men exposed to early life trauma also display reduced sperm levels of miR-34/449. And here we show that miR-34c can also increase the expression of its own gene, and that of miR-449 in human embryonic stem cells, suggesting that human PIEs derived from men with low sperm miR-34/449 levels may also contain this potentially harmful defect.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2346694"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MK-801-exposure induces increased translation efficiency and mRNA hyperacetylation of Grin2a in the mouse prefrontal cortex. MK-801 暴露诱导小鼠前额叶皮层中 Grin2a 的翻译效率提高和 mRNA 过度乙酰化。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-10-26 DOI: 10.1080/15592294.2024.2417158

Liting Xue, Jialu Zhao, Xu Liu, Tian Zhao, Ying Zhang, Haihong Ye

{"title":"MK-801-exposure induces increased translation efficiency and mRNA hyperacetylation of Grin2a in the mouse prefrontal cortex.","authors":"Liting Xue, Jialu Zhao, Xu Liu, Tian Zhao, Ying Zhang, Haihong Ye","doi":"10.1080/15592294.2024.2417158","DOIUrl":"10.1080/15592294.2024.2417158","url":null,"abstract":"Acute exposure to MK-801, the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, induces schizophrenia-like behavioural changes in juvenile male mice. However, the effects of acute MK-801 exposure on brain gene expression at the translation level remain unclear. Here, we conducted ribosome profiling analysis on the prefrontal cortex (PFC) of acute MK-801-exposed juvenile male mice. We found 357 differentially translated genes, with the N4-acetylcytidine (ac4C) consensus motif enriched in the transcripts with increased translation efficiency. Acetylated RNA immunoprecipitation sequencing revealed 148 differentially acetylated peaks, of which 121 were hyperacetylated, and 27 were hypoacetylated. Genes harbouring these peaks were enriched in pathways related to axon guidance, Hedgehog signalling pathway, neuron differentiation, and memory. Grin2a encodes an NMDA receptor subunit NMDAR2A, and its human orthologue is a strong susceptibility gene for schizophrenia. Grin2a mRNA was hyperacetylated and exhibited significantly increased translation efficiency. NMDAR2A protein level was increased in MK-801-exposed PFC. Pretreatment of Remodelin, an inhibitor of N-acetyltransferase 10, returned the NMDAR2A protein levels to normal and partially reversed schizophrenia-like behaviours of MK-801-exposed mice, shedding light on the possible role of mRNA acetylation in the aetiology of schizophrenia.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2417158"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasma methylated GNB4 and Riplet as a novel dual-marker panel for the detection of hepatocellular carcinoma. 血浆甲基化 GNB4 和 Riplet 作为检测肝细胞癌的新型双标记物面板。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2023-12-28 DOI: 10.1080/15592294.2023.2299044

Yanteng Zhao, Lei Zhao, Huifang Jin, Ying Xie, Liyinghui Chen, Wei Zhang, Lanlan Dong, Lianglu Zhang, Yue Huang, Kangkang Wan, Qiankun Yang, Shaochi Wang

{"title":"Plasma methylated GNB4 and Riplet as a novel dual-marker panel for the detection of hepatocellular carcinoma.","authors":"Yanteng Zhao, Lei Zhao, Huifang Jin, Ying Xie, Liyinghui Chen, Wei Zhang, Lanlan Dong, Lianglu Zhang, Yue Huang, Kangkang Wan, Qiankun Yang, Shaochi Wang","doi":"10.1080/15592294.2023.2299044","DOIUrl":"10.1080/15592294.2023.2299044","url":null,"abstract":"Early detection of hepatocellular carcinoma (HCC) can greatly improve the survival rate of patients. We aimed to develop a novel marker panel based on cell-free DNA (cfDNA) methylation for the detection of HCC. The differentially methylated CpG sites (DMCs) specific for HCC blood diagnosis were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then validated by the whole genome bisulphite sequencing (WGBS) of 12 paired HCC and paracancerous tissues. The clinical performance of the panel was evaluated using tissue samples [32 HCC, chronic liver disease (CLD), and healthy individuals] and plasma cohorts (173 HCC, 199 CLD, and 98 healthy individuals). The combination of G protein subunit beta 4 (GNB4) and Riplet had the optimal area under the curve (AUC) in seven candidates through TCGA, GEO, and WGBS analyses. In tissue validation, the GNB4 and Riplet showed an AUC of 100% with a sensitivity and specificity of 100% for detecting any-stage HCC. In plasma, it demonstrated a high sensitivity of 84.39% at 91.92% specificity, with an AUC of 92.51% for detecting any-stage HCC. The dual-marker panel had a higher sensitivity of 78.26% for stage I HCC than alpha-fetoprotein (AFP) of 47.83%, and a high sensitivity of 70.27% for detecting a single tumour (size ≤3 cm). In conclusion, we developed a novel dual-marker panel that demonstrates high accuracy in detecting HCC, surpassing the performance of AFP testing.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2299044"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction. 更正。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-08-04 DOI: 10.1080/15592294.2024.2388387

引用次数: 0

Global DNA methylation is not elevated in blood samples from Machado-Joseph disease mutation carriers. 在马查多-约瑟夫病突变携带者的血液样本中，全局 DNA 甲基化没有升高。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-06-20 DOI: 10.1080/15592294.2024.2368995

Luís Teves, Ana Rosa Vieira Melo, Ana F Ferreira, Mafalda Raposo, Carolina Lemos, Conceição Bettencourt, Manuela Lima

{"title":"Global DNA methylation is not elevated in blood samples from Machado-Joseph disease mutation carriers.","authors":"Luís Teves, Ana Rosa Vieira Melo, Ana F Ferreira, Mafalda Raposo, Carolina Lemos, Conceição Bettencourt, Manuela Lima","doi":"10.1080/15592294.2024.2368995","DOIUrl":"10.1080/15592294.2024.2368995","url":null,"abstract":"Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia (SCA) caused by a polyglutamine expansion in the ataxin-3 protein, which initiates a cascade of pathogenic events, including transcriptional dysregulation. Genotype-phenotype correlations in MJD are incomplete, suggesting an influence of additional factors, such as epigenetic modifications, underlying the MJD pathogenesis. DNA methylation is known to impact the pathophysiology of neurodegenerative disorders through gene expression regulation and increased methylation has been reported for other SCAs. In this work we aimed to analyse global methylation in MJD carriers. Global 5-mC levels were quantified in blood samples of 33 MJD mutation carriers (patients and preclinical subjects) and 33 healthy controls, matched by age, sex, and smoking status. For a subset of 16 MJD subjects, a pilot follow-up analysis with two time points was also conducted. No differences were found in median global 5-mC levels between MJD mutation carriers and controls and no correlations between methylation levels and clinical or genetic variables were detected. Also, no alterations in global 5-mC levels were observed over time. Our findings do not support an increase in global blood methylation levels associated with MJD.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2368995"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitors. 药物治疗后 HDAC 和 SIRT 基因表达的变化与癌细胞系对激酶抑制剂敏感性的关系。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-02-18 DOI: 10.1080/15592294.2024.2309824

Julia Krushkal, Yingdong Zhao, Kyle Roney, Weimin Zhu, Alan Brooks, Deborah Wilsker, Ralph E Parchment, Lisa M McShane, James H Doroshow

{"title":"Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitors.","authors":"Julia Krushkal, Yingdong Zhao, Kyle Roney, Weimin Zhu, Alan Brooks, Deborah Wilsker, Ralph E Parchment, Lisa M McShane, James H Doroshow","doi":"10.1080/15592294.2024.2309824","DOIUrl":"10.1080/15592294.2024.2309824","url":null,"abstract":"Histone deacetylases (HDACs) and sirtuins (SIRTs) are important epigenetic regulators of cancer pathways. There is a limited understanding of how transcriptional regulation of their genes is affected by chemotherapeutic agents, and how such transcriptional changes affect tumour sensitivity to drug treatment. We investigated the concerted transcriptional response of HDAC and SIRT genes to 15 approved antitumor agents in the NCI-60 cancer cell line panel. Antitumor agents with diverse mechanisms of action induced upregulation or downregulation of multiple HDAC and SIRT genes. HDAC5 was upregulated by dasatinib and erlotinib in the majority of the cell lines. Tumour cell line sensitivity to kinase inhibitors was associated with upregulation of HDAC5, HDAC1, and several SIRT genes. We confirmed changes in HDAC and SIRT expression in independent datasets. We also experimentally validated the upregulation of HDAC5 mRNA and protein expression by dasatinib in the highly sensitive IGROV1 cell line. HDAC5 was not upregulated in the UACC-257 cell line resistant to dasatinib. The effects of cancer drug treatment on expression of HDAC and SIRT genes may influence chemosensitivity and may need to be considered during chemotherapy.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2309824"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Homocysteine affects macrophage polarization by altering m6A methylation of scavenger receptors CD209 and CD163L1.

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-12-03 DOI: 10.1080/15592294.2024.2437272

Yu Liang, Yongbo Wang, Jia Tan, Jingxuan Shu, Ya Xu, Mingyuan Wang, Shengjun Yang, Linna Ma

{"title":"Homocysteine affects macrophage polarization by altering m6A methylation of scavenger receptors CD209 and CD163L1.","authors":"Yu Liang, Yongbo Wang, Jia Tan, Jingxuan Shu, Ya Xu, Mingyuan Wang, Shengjun Yang, Linna Ma","doi":"10.1080/15592294.2024.2437272","DOIUrl":"10.1080/15592294.2024.2437272","url":null,"abstract":"Atherosclerosis is a chronic inflammatory disease characterized by fatty plaque deposits on artery walls. Elevated plasma homocysteine (Hcy) levels are an independent risk factor for atherosclerosis. Research on the mechanism by which Hcy promotes atherosclerosis has gradually turned to epigenetic inheritance, but the correlation between Hcy and m6A (N6-methyladenosine) modification has not been reported. In this study, MeRIP-seq was performed on macrophages and Hcy-treated macrophages. GO and KEGG analyses were used to perform functional analysis of differentially methylated genes. qRT-PCR and western blot were taken to determine the expression of CD209, CD163L1, proinflammatory, and anti-inflammatory factors. Flow cytometry was used to detect the proportion of M2 macrophages. The results showed that after Hcy treatment, the overall m6A methylation of macrophages was down-regulated, and 856 differential methylation peaks were annotated to 781 genes. These included CD209 and CD163L1, whose m6A methylation was inhibited after treatment with Hcy. In addition, mRNA and protein expressions of CD209 and CD163L1 were also inhibited after Hcy treatment. Overexpression of CD209 or CD163L1 prevents the Hcy-induced decrease in the proportion of M2 macrophages. This article identified changes in the modification level of m6A in macrophages by Hcy and revealed the possible mechanism by which Hcy induces macrophage polarization.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2437272"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ZSCAN25 methylation predicts seizures and severe alcohol withdrawal syndrome. ZSCAN25 甲基化可预测癫痫发作和严重酒精戒断综合征。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-01-03 DOI: 10.1080/15592294.2023.2298057

Allan Andersen, Emily Milefchik, Emma Papworth, Brandan Penaluna, Kelsey Dawes, Joanna Moody, Gracie Weeks, Ellyse Froehlich, Kaitlyn deBlois, Jeffrey D Long, Robert Philibert

{"title":"ZSCAN25 methylation predicts seizures and severe alcohol withdrawal syndrome.","authors":"Allan Andersen, Emily Milefchik, Emma Papworth, Brandan Penaluna, Kelsey Dawes, Joanna Moody, Gracie Weeks, Ellyse Froehlich, Kaitlyn deBlois, Jeffrey D Long, Robert Philibert","doi":"10.1080/15592294.2023.2298057","DOIUrl":"10.1080/15592294.2023.2298057","url":null,"abstract":"Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown. To determine this, we first conducted genome-wide DNA methylation analyses of subjects entering and exiting alcohol treatment to identify loci whose methylation quickly reverted as a function of abstinence. We then tested whether methylation at a rapidly reverting locus, cg07375256, or other existing metrics including PAWSS scores, CDT levels, or ATS, could predict outcome in 125 subjects admitted for consideration of AWS. We found that PAWSS did not significantly predict severe AWS nor seizures. However, methylation at cg07375256 (ZSCAN25) and CDT strongly predicted severe AWS with ATS (p < 0.007) and cg07375256 (p < 6 × 10-5) methylation also predicting AWS associated seizures. We conclude that epigenetic methods can predict those likely to experience severe AWS and that the use of these or similar Precision Epigenetic approaches could better guide AWS management.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2298057"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10766392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A promising application of kidney-specific cell-free DNA methylation markers in real-time monitoring sepsis-induced acute kidney injury. 肾脏特异性无细胞 DNA 甲基化标记在实时监测败血症诱发的急性肾损伤中的应用前景广阔。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-10-07 DOI: 10.1080/15592294.2024.2408146

Ruilian You, Xiangming Quan, Peng Xia, Chao Zhang, Anlei Liu, Hanshu Liu, Ling Yang, Huadong Zhu, Limeng Chen

{"title":"A promising application of kidney-specific cell-free DNA methylation markers in real-time monitoring sepsis-induced acute kidney injury.","authors":"Ruilian You, Xiangming Quan, Peng Xia, Chao Zhang, Anlei Liu, Hanshu Liu, Ling Yang, Huadong Zhu, Limeng Chen","doi":"10.1080/15592294.2024.2408146","DOIUrl":"10.1080/15592294.2024.2408146","url":null,"abstract":"Sepsis-induced acute kidney injury (SI-AKI) is a common clinical syndrome that is associated with high mortality and morbidity. Effective timely detection may improve the outcome of SI-AKI. Kidney-derived cell-free DNA (cfDNA) may provide new insight into understanding and identifying SI-AKI. Plasma cfDNA from 82 healthy individuals, 7 patients with sepsis non-acute kidney injury (SN-AKI), and 9 patients with SI-AKI was subjected to genomic methylation sequencing. We deconstructed the relative contribution of cfDNA from different cell types based on cell-specific methylation markers and focused on exploring the association between kidney-derived cfDNA and SI-AKI.Based on the deconvolution of the cfDNA methylome: SI-AKI patients displayed the elevated cfDNA concentrations with an increased contribution of kidney epithelial cells (kidney-Ep) DNA; kidney-Ep derived cfDNA achieved high accuracy in distinguishing SI-AKI from SN-AKI (AUC = 0.92, 95% CI 0.7801-1); the higher kidney-ep cfDNA concentrations tended to correlate with more advanced stages of SI-AKI; strikingly, SN-AKI patients with potential kidney damage unmet by SI-AKI criteria showed higher levels of kidney-Ep derived cfDNA than healthy individuals. The autonomous screening of kidney-Ep (n = 24) and kidney endothelial (kidney-Endo, n = 12) specific methylation markers indicated the unique identity of kidney-Ep/kidney-Endo compared with other cell types, and its targeted assessment reproduced the main findings of the deconvolution of the cfDNA methylome. Our study first demonstrates that kidney-Ep- and kidney-Endo-specific methylation markers can serve as a novel marker for SI-AKI emergence, supporting further exploration of the utility of kidney-specific cfDNA methylation markers in the study of SI-AKI.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2408146"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0