Cancer Treatment Reviews, Journal Year: 2024, Volume and Issue: 128, P. 102763 - 102763
Published: May 16, 2024
Language: Английский
Genome Medicine, Journal Year: 2023, Volume and Issue: 15(1)
Published: May 3, 2023
Epigenetic characterization of cell-free DNA (cfDNA) is an emerging approach for detecting and characterizing diseases such as cancer. We developed a strategy using nanopore-based single-molecule sequencing to measure cfDNA methylomes. This generated up 200 million reads single sample from cancer patients, order magnitude improvement over existing nanopore methods. classifier determine whether individual originated tumor or immune cells. Leveraging methylomes matched tumors cells, we characterized patients longitudinal monitoring during treatment.
Language: Английский
Citations
36
Cell Genomics, Journal Year: 2024, Volume and Issue: 4(6), P. 100421 - 100421
Published: May 1, 2024
Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, RNA-seq datasets from eight control endurance exercise-trained (EET) rats. Integration of baseline mapped gene location dependence epigenetic features identified differing regulatory landscapes in each tissue. The transcriptional responses to 8 weeks EET showed little overlap predominantly comprised tissue-type enriched genes. We sex differences transcriptomic epigenomic changes induced by EET. However, sex-biased were linked shared signaling pathways. found that G protein-coupled receptor-encoding genes are regulated EET, suggesting a role for these receptors adaptations training tissues. Our findings provide new insights into underlying EET-induced benefits organs.
Language: Английский
Citations
14
Biology, Journal Year: 2025, Volume and Issue: 14(1), P. 98 - 98
Published: Jan. 19, 2025
Neurodegenerative diseases are characterized by profound differences between females and males in terms of incidence, clinical presentation, disease progression. Furthermore, there is evidence suggesting that sensitivity to medical treatments may exist the two sexes. Although role sex hormones chromosomes driving differential susceptibility these well-established, molecular alterations underlying remain poorly understood. Epigenetic mechanisms, including DNA methylation, histone tail modifications, activity non-coding RNAs, strongly implicated pathogenesis neurodegenerative diseases. While it known epigenetic mechanisms play a crucial sexual differentiation distinct patterns characterize males, sex-specific have been largely overlooked studies aiming identify associated with This review aims provide an overview processes central nervous system, main three diseases, Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis. Understanding sex-related essential for developing personalized interventions account unique landscapes each sex.
Language: Английский
Citations
1
Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15
Published: Feb. 6, 2025
Triple-negative breast cancer (TNBC) is an aggressive subtype of characterized by the lack estrogen receptor (ER), progesterone (PR), and human epidermal growth factor 2 (HER2). Chemotherapy remains primary treatment option, yet TNBC frequently develops resistance, leading to relapse metastasis. Emerging evidence highlights potential combining DNA methylation inhibitors with immune checkpoint (ICIs). contributes escape silencing immune-regulatory genes, thereby reducing tumor's visibility cells. Reversing this epigenetic modification can reinvigorate surveillance enhance efficacy immunotherapies. This review discusses role in progression evasion, focusing on recent advances combination therapies involving ICIs. We discuss underlying mechanisms that enable these therapeutic synergies, preclinical clinical supporting approach, challenges posed tumor heterogeneity, drug toxicity. Finally, we explore for personalized strategies incorporating multi-omics data optimize outcomes. The integration immunotherapy offers a promising avenue improving survival patients.
Language: Английский
Citations
1
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: March 4, 2025
Introduction The HIV regulatory protein Tat enhances viral transcription and also modifies host gene expression, affecting cell functions like cycle apoptosis. Residual expression of is detected in blood other tissues even under antiretroviral treatment. Cohort studies have indicated that, despite virologic suppression, people with (PWH) are at increased risk comorbidities linked to chronic inflammation, accelerated immune ageing, cellular senescence, sometimes associated abnormal genomic methylation patterns. We analysed whether influences DNA subsequently impacts the transcriptional signature, contributing inflammation ageing. Methods transfected Jurkat cells full-length (Tat101), Tat’s first exon (Tat72), or an empty vector (TetOFF). assessed modifications via Infinium MethylationEPIC array, we evaluated transcriptomic alterations through RNA-Seq. Methylation levels promoters body regions were correlated their data, subsequently, performed overrepresentation analysis identify biological terms containing differentially methylated expressed genes. Results Tat101 caused significant hyper- hypomethylation changes individual CpG sites, resulting slightly global hypermethylation. bodies resulted altered specifically regulating 5.1% genes (DEGs) Tat101- expressing cells. In contrast, Tat72 had a minimal impact on this epigenetic process. observed involved inflammatory responses, lipid antigen presentation, Discussion infection may constitute key modelling actor that contributes pathogenesis inflammation. Clinical interventions targeting blockade reduce senescence related comorbidities.
Language: Английский
Citations
1
Genome Research, Journal Year: 2025, Volume and Issue: 35(4), P. 545 - 558
Published: April 1, 2025
Over the past decade, long-read sequencing has evolved into a pivotal technology for uncovering hidden and complex regions of genome. Significant cost efficiency, scalability, accuracy advancements have driven this evolution. Concurrently, novel analytical methods emerged to harness full potential long reads. These enabled milestones such as first fully completed human genome, enhanced identification understanding genomic variants, deeper insights interplay between epigenetics variation. This mini-review provides comprehensive overview latest developments in DNA analysis, encompassing reference-based de novo assembly approaches. We explore entire workflow, from initial data processing variant calling annotation, focusing on how these improve our ability interpret wide array variants. Additionally, we discuss current challenges, limitations, future directions field, offering detailed examination state-of-the-art bioinformatics sequencing.
Language: Английский
Citations
1
Current Oncology, Journal Year: 2024, Volume and Issue: 31(1), P. 482 - 500
Published: Jan. 13, 2024
DNA methylation is a fundamental mechanism of epigenetic control in cells and its dysregulation strongly implicated cancer development. Cancers possess an extensively hypomethylated genome with focal regions hypermethylation at CPG islands. Due to the highly conserved nature cancer-specific methylation, detection cell-free plasma using liquid biopsies constitutes area interest biomarker research. The advent next-generation sequencing newer computational technologies have allowed for development diagnostic prognostic biomarkers that utilize profiling diagnose disease stratify risk. Methylome-based predictive can determine response anti-cancer therapy. An additional emerging application these minimal residual monitoring. Several key challenges need be addressed before cfDNA-based become fully integrated into practice. first relates biology stability cfDNA. second concerns clinical validity generalizability methylation-based assays, many which are type-specific. third involves their practicability, stumbling block translating from bench clinic. Future work on developing pan-cancer assays respective validities confirmed well-designed, prospective trials crucial pushing greater use tools oncology.
Language: Английский
Citations
7
Genome biology, Journal Year: 2024, Volume and Issue: 25(1)
Published: April 5, 2024
Abstract Background DNA methylation is an essential epigenetic modification. However, its contribution to trait changes and diversity in the domestication of perennial fruit trees remains unknown. Results Here, we investigate variation during pear improvement using whole-genome bisulfite sequencing 41 accessions. Contrary significant decrease rice domestication, detect a global increase improvement. We find this specific significantly correlated with downregulation Demeter-like1 ( DML1 , encoding demethylase) due human selection. identify total 5591 differentially methylated regions (DMRs). Methylation CG CHG contexts undergoes co-evolution DMRs have higher genetic than selection sweep regions, especially introns. Approximately 97% are not associated any SNPs, these starch sucrose metabolism phenylpropanoid biosynthesis. also perform correlation analysis between gene expression. genes close hypermethylated that ripening. further verify function hyper-DMR-associated gene, CAMTA2 demonstrate overexpression tomato callus inhibits Conclusions Our study describes pattern tree suggests increased plays role early ripening fruits.
Language: Английский
Citations
6
Cell Genomics, Journal Year: 2024, Volume and Issue: 4(11), P. 100674 - 100674
Published: Oct. 14, 2024
The Long-Read Personalized OncoGenomics (POG) dataset comprises a cohort of 189 patient tumors and 41 matched normal samples sequenced using the Oxford Nanopore Technologies PromethION platform. This from POG program Marathon Hope Cancer Centres Network includes DNA RNA short-read sequence data, analytics, clinical information. We show potential long-read sequencing for resolving complex cancer-related structural variants, viral integrations, extrachromosomal circular DNA. Long-range phasing facilitates discovery allelically differentially methylated regions (aDMRs) allele-specific expression, including recurrent aDMRs in cancer genes RET CDKN2A. Germline promoter methylation MLH1 can be directly observed Lynch syndrome. Promoter BRCA1 RAD51C is likely driver behind homologous recombination deficiency where no coding mutation was found. demonstrates applications precision medicine available as resource developing analytical approaches this technology.
Language: Английский
Citations
6
Epigenomes, Journal Year: 2024, Volume and Issue: 8(1), P. 4 - 4
Published: Jan. 26, 2024
While studying myoblast methylomes and transcriptomes, we found that CDH15 had a remarkable preference for expression in both myoblasts cerebellum. To understand how widespread such relationship was its epigenetic biological correlates, systematically looked genes with similar transcription profiles analyzed their DNA methylation chromatin state accessibility many different cell populations. Twenty were expressed preferentially cerebellum (Myob/Cbl genes). Some shared hypo- or hypermethylated regions Particularly striking ZNF556, whose promoter is hypomethylated expressing cells but highly methylated the populations do not express gene. In reporter gene assays, demonstrated promoter’s activity sensitive. The atypical epigenetics of ZNF556 may have originated from hypomethylation selective activation sperm progenitors oocytes. Five Myob/Cbl (KCNJ12, ST8SIA5, ZIC1, VAX2, EN2) much higher RNA levels than displayed myoblast-specific hypermethylation upstream and/or downstream promoters downmodulate expression. Differential associated alternative usage MCF2L, DOK7, CNPY1, ANK1. PAX3, LBX1, EN2, VAX2 encode sequence-specific factors, which likely help drive specificity other genes. This study extends our understanding epigenetic/transcription associations related to differentiation elucidate relationships between signatures muscular dystrophies cerebellar-linked neuropathologies.
Language: Английский
Citations
5