'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Fri, 21 Feb 2025 16:02:57 EST Fri, 21 Feb 2025 16:02:57 EST jirtle@radonc.duke.edu james001@jirtle.com EpiBrCan-Lite: A lightweight deep learning model for breast cancer subtype classification using epigenomic data. Bedi P, Rani S, Gupta B, Bhasin V, Gole P
Comput Methods Programs Biomed (Mar 2025)

Early breast cancer subtypes classification improves the survival rate as it facilitates prognosis of the patient. In literature this problem was prominently solved by various Machine Learning and Deep Learning techniques. However, these studies have three major shortcomings: huge Trainable Weight Parameters (TWP), suffer from low performance and class imbalance problem.]]> Wed, 31 Dec 1969 19:00:00 EST Genetics of Prader-Willi and Angelman syndromes: 2024 update. Godler DE, Singh D, Butler MG
Curr Opin Psychiatry (Mar 2025)

Prader-Willi (PWS) and Angelman (AS) syndromes arise from errors in 15q11-q13 imprinting. This review describes recent advances in genomics and how these expand our understanding of these rare disorders, guiding treatment strategies to improve patient outcomes.]]> Wed, 31 Dec 1969 19:00:00 EST Long non coding RNA function in epigenetic memory with a particular emphasis on genomic imprinting and X chromosome inactivation. Le LTT
Gene (Apr 2025)

Cells preserve and convey certain gene expression patterns to their progeny through the mechanism called epigenetic memory. Epigenetic memory, encoded by epigenetic markers and components, determines germline inheritance, genomic imprinting, and X chromosome inactivation. First discovered long non coding RNAs were implicated in genomic imprinting and X-inactivation and these two phenomena clearly demonstrate the role of lncRNAs in epigenetic memory regulation. Undoubtedly, lncRNAs are well-suited for regulating genes in close proximity at imprinted loci. Due to prolonged association with the transcription site, lncRNAs are able to guide chromatin modifiers to certain locations, thereby enabling accurate temporal and spatial regulation. Nevertheless, the current state of knowledge regarding lncRNA biology and imprinting processes is still in its nascent phase. Herein, we provide a synopsis of recent scientific advancements to enhance our comprehension of lncRNAs and their functions in epigenetic memory, with a particular emphasis on genomic imprinting and X chromosome inactivation, thus gaining a deeper understanding of the role of lncRNAs in epigenetic regulatory networks.]]> Wed, 31 Dec 1969 19:00:00 EST How omics is revealing new roles for glia in addiction. Bergkamp DJ, Neumaier JF
Glia (Mar 2025)

Experiments to study the biology of addiction have historically focused on the mechanisms through which drugs of abuse drive changes in the functioning of neurons and neural circuits. Glia have often been ignored in these studies, however, and this has left many questions in the field unanswered, particularly, surrounding how glia contribute to changes in synaptic plasticity, regulation of neuroinflammation, and functioning of neural ensembles given massive changes in signaling across the CNS. Omics methods (transcriptomics, translatomics, epigenomics, proteomics, metabolomics, and others) have expanded researchers' abilities to generate hypotheses and carry out mechanistic studies of glial cells during acquisition of drug taking, intoxication, withdrawal, and relapse to drug seeking. Here, we present a survey of how omics technological advances are revising our understanding of astrocytes, microglia, oligodendrocytes, and ependymal cells in addiction biology.]]> Wed, 31 Dec 1969 19:00:00 EST Extensive epigenomic dysregulation is a hallmark of homologous recombination deficiency in triple-negative breast cancer. Chen Y, Salas LA, Marotti JD, Jenkins NP, Cheng C, Miller TW, Kettenbach AN, Christensen BC
Int J Cancer (Mar 2025)

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with substantial disease heterogeneity, limited treatment options, and dismal clinical outcomes. Some TNBCs display homologous recombination deficiency (HRD), a phenotype with elevated genomic burden and worse prognosis if left untreated but chemotherapeutic sensitivity. While the molecular landscape of TNBC is distinct from other breast cancer subtypes, the TNBC-specific link between HRD and epigenome-wide methylation has not been established. This study reports two independent cohorts of TNBC tumors (n = 32 and n = 58) with HRD and epigenomic landscapes measured by the Multiplex Ligation-dependent Probe Amplification assay and the Illumina MethylationEPIC arrays, respectively. Genome-wide copy number and methylation alterations were significantly higher in HRD (all p <.05). Methylation of genome-wide repeat element Alu and transcriptional regulatory regions were significantly lower in HRD (all p <.05). An age-adjusted epigenome-wide association study of the continuous HRD probability scores revealed significant loci (all FDR <0.05) that were depleted from the CpG-rich "island" regions often seen in gene promoters but enriched in the CpG-poor "open sea" regions localized to gene enhancers. The significant loci implicated well-known candidate genes involved in the epithelial-to-mesenchymal transition, Wnt signaling, and DNA damage response. Supervised machine learning of HRD with nucleotide-specific methylation as the input enabled clinically relevant tumor stratification. Taken together, this study provides novel biological and translational insights into HRD in TNBCs.]]> Wed, 31 Dec 1969 19:00:00 EST Microglial Responses to Alzheimer's Disease Pathology: Insights From "Omics" Studies. Reid AN, Jayadev S, Prater KE
Glia (Mar 2025)

Human genetics studies lent firm evidence that microglia are key to Alzheimer's disease (AD) pathogenesis over a decade ago following the identification of AD-associated genes that are expressed in a microglia-specific manner. However, while alterations in microglial morphology and gene expression are observed in human postmortem brain tissue, the mechanisms by which microglia drive and contribute to AD pathology remain ill-defined. Numerous mouse models have been developed to facilitate the disambiguation of the biological mechanisms underlying AD, incorporating amyloidosis, phosphorylated tau, or both. Over time, the use of multiple technologies including bulk tissue and single cell transcriptomics, epigenomics, spatial transcriptomics, proteomics, lipidomics, and metabolomics have shed light on the heterogeneity of microglial phenotypes and molecular patterns altered in AD mouse models. Each of these 'omics technologies provide unique information and biological insight. Here, we review the literature on the approaches and findings of these methods and provide a synthesis of the knowledge generated by applying these technologies to mouse models of AD.]]> Wed, 31 Dec 1969 19:00:00 EST DNA Methylation and Target Gene Expression in Fatty Liver Progression From Simple Steatosis to Advanced Fibrosis. Li J, Liu X, Tran TT, Lee M, Tsai RYL
Liver Int (Mar 2025)

Metabolic dysfunction-associated steatotic liver diseases (MASLD), also known as non-alcoholic fatty liver diseases (NAFLD), have become a leading risk factor for hepatocellular carcinoma (HCC) in Western countries. NAFLD progresses from simple steatosis to HCC, with advanced liver fibrosis (ALF) and metabolic dysfunction-associated steatohepatitis (MASH) or non-alcoholic steatohepatitis (NASH) representing the two preceding high-risk stages.]]> Wed, 31 Dec 1969 19:00:00 EST Multi Layered Omics Approaches Reveal Glia Specific Alterations in Alzheimer's Disease: A Systematic Review and Future Prospects. İş Ã–, Min Y, Wang X, Oatman SR, Abraham Daniel A, Ertekin-Taner N
Glia (Mar 2025)

Alzheimer's disease (AD) is the most common neurodegenerative dementia with multi-layered complexity in its molecular etiology. Multiple omics-based approaches, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, and lipidomics are enabling researchers to dissect this molecular complexity, and to uncover a plethora of alterations yielding insights into the pathophysiology of this disease. These approaches reveal multi-omics alterations essentially in all cell types of the brain, including glia. In this systematic review, we screen the literature for human studies implementing any omics approach within the last 10 years, to discover AD-associated molecular perturbations in brain glial cells. The findings from over 200 AD-related studies are reviewed under four different glial cell categories: microglia, oligodendrocytes, astrocytes and brain vascular cells. Under each category, we summarize the shared and unique molecular alterations identified in glial cells through complementary omics approaches. We discuss the implications of these findings for the development, progression and ultimately treatment of this complex disease as well as directions for future omics studies in glia cells.]]> Wed, 31 Dec 1969 19:00:00 EST Family study of bipolar disorder with comorbid anxiety disorder points to with possible role of parent-of-origin effect. Maki H, Sakai N, Kataoka M, Fujii K, Kageyama Y, Hayama T, Matsuo K, Nishioka M, Kato T
PCN Rep (Mar 2025)

The aim of this study was to provide new insights into the genetics of bipolar disorder (BD) by analyzing BD comorbid with anxiety disorders.]]> Wed, 31 Dec 1969 19:00:00 EST Host-microbe multi-omics and succinotype profiling have prognostic value for future relapse in patients with inflammatory bowel disease. O'Sullivan J, Patel S, Leventhal GE, Fitzgerald RS, Laserna-Mendieta EJ, Huseyin CE, Konstantinidou N, Rutherford E, Lavelle A, Dabbagh K, DeSantis TZ, Shanahan F, Temko A, Iwai S, Claesson MJ
Gut Microbes (Dec 2025)

Crohn's disease (CD) and ulcerative colitis (UC) are chronic relapsing inflammatory bowel disorders (IBD), the pathogenesis of which is uncertain but includes genetic susceptibility factors, immune-mediated tissue injury and environmental influences, most of which appear to act via the gut microbiome. We hypothesized that host-microbe alterations could be used to prognostically stratify patients experiencing relapses up to four years after endoscopy. We therefore examined multiple omics data, including published and new datasets, generated from paired inflamed and non-inflamed mucosal biopsies from 142 patients with IBD (54 CD; 88 UC) and from 34 control (non-diseased) biopsies. The relapse-predictive potential of 16S rRNA gene and transcript amplicons (standing and active microbiota) were investigated along with host transcriptomics, epigenomics and genetics. While standard single-omics analysis could not distinguish between patients who relapsed and those that remained in remission within four years of colonoscopy, we did find an association between the number of flares and a patient's succinotype. Our multi-omics machine learning approach was also able to predict relapse when combining features from the microbiome and human host. Therefore multi-omics, rather than single omics, better predicts relapse within 4 years of colonoscopy, while a patient's succinotype is associated with a higher frequency of relapses.]]> Wed, 31 Dec 1969 19:00:00 EST Mediation of Social Determinants and Hypertension by Epigenetic Age in CARDIA. Szeto MD, Ning H, Pedamallu H, Zheng Y, Schneper L, Joyce B, Kim K, Kershaw KN, Reges O, Hou L, Allen NB, Notterman DA, Lloyd-Jones DM
Hypertension (Mar 2025)

]]> Wed, 31 Dec 1969 19:00:00 EST Long-read structural and epigenetic profiling of a kidney tumor-matched sample with nanopore sequencing and optical genome mapping. Margalit S, Tulpová Z, Detinis Zur T, Michaeli Y, Deek J, Nifker G, Haldar R, Gnatek Y, Omer D, Dekel B, Baris Feldman H, Grunwald A, Ebenstein Y
NAR Genom Bioinform (Mar 2025)

Carcinogenesis often involves significant alterations in the cancer genome, marked by large structural variants (SVs) and copy number variations (CNVs) that are difficult to capture with short-read sequencing. Traditionally, cytogenetic techniques are applied to detect such aberrations, but they are limited in resolution and do not cover features smaller than several hundred kilobases. Optical genome mapping (OGM) and nanopore sequencing [Oxford Nanopore Technologies (ONT)] bridge this resolution gap and offer enhanced performance for cytogenetic applications. Additionally, both methods can capture epigenetic information as they profile native, individual DNA molecules. We compared the effectiveness of the two methods in characterizing the structural, copy number and epigenetic landscape of a clear cell renal cell carcinoma tumor. Both methods provided comparable results for basic karyotyping and CNVs, but differed in their ability to detect SVs of different sizes and types. ONT outperformed OGM in detecting small SVs, while OGM excelled in detecting larger SVs, including translocations. Differences were also observed among various ONT SV callers. Additionally, both methods provided insights into the tumor's methylome and hydroxymethylome. While ONT was superior in methylation calling, hydroxymethylation reports can be further optimized. Our findings underscore the importance of carefully selecting the most appropriate platform based on specific research questions.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenomic Changes in Ostrinia Moths Under Elevated Pupal and Adult Temperature. Velikaneye BA, Kozak GM
Mol Ecol (Mar 2025)

Epigenetic changes in the methylation of DNA may occur in response to environmental stressors, including warming climates. DNA methylation may also play an important role in regulating gene expression during both male and female reproduction in many insect species. However, it is currently unknown how DNA methylation shifts when individuals are reproducing under warmer temperatures. We exposed European corn borer moths (Ostrinia nubilalis) to heat during the pupal and adult life stages then investigated changes in DNA methylation across the genome using enzymatic methyl-seq (EM-seq). We compared methylation patterns in reproductive males and females exposed to heat (28°C) to those that experienced an ambient temperature (23°C). We found that heat exposure led to a small but significant increase in the percentage of methylated CpG sites throughout the genome in both sexes. However, DNA methylation rates were higher in females and differential methylation following heat exposure localised to unique regions in each sex. In males, methylation shifted within genes belonging to pathways including Hippo signalling, ubiquitin-mediated proteolysis, DNA damage repair and spermatogenesis. In females, differential methylation occurred in genes related to histone modification and oogenesis. Our results suggest that DNA methylation patterns respond to moderate heat exposure in Lepidoptera and provide insight into epigenetic responses to heatwaves, suggesting novel pathways that may be involved in responding to heat stress during metamorphosis and reproduction.]]> Wed, 31 Dec 1969 19:00:00 EST Renal Juxtaglomerular Cell Tumors Exhibit Distinct Genomic and Epigenomic Features and Lack Recurrent Gene Fusions: Comprehensive Molecular Analysis of a Multi-institutional Series. Michalova K, Martinek P, Mezencev R, Gupta S, Williamson S, Wasco M, Mohanty S, Magi-Galluzzi C, Cañete-Portillo S, Aron M, Kandukuri S, Lobo J, Barkan GA, Kilic I, Strakova-Peterikova A, Pivovarcikova K, Michal M, Michal M, Ulbright TM, Acosta AM
Am J Surg Pathol (Mar 2025)

Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent. Recently, whole-genome analysis identified alterations involving genes of MAPK-RAS pathway in a subset, but no major pathogenic alterations have been discovered in prior whole transcriptome analyses. Considering the limited understanding of the molecular features of JxGCTs, we sought to assess a collaborative series with a multiomic approach to further define the molecular characteristics of this entity. Fifteen tumors morphologically compatible with JxGCTs were evaluated using immunohistochemistry for renin, single-nucleotide polymorphism array (SNP), low-pass whole-genome sequencing, and RNA sequencing (fusion assay). In addition, methylation analysis comparing JxGCT, GT, and SFT was performed. All cases tested with renin (n=11) showed positive staining. Multiple chromosomal abnormalities were identified in all cases analyzed (n=8), with gains of chromosomes 1p, 10, 17, and 19 and losses of chromosomes 9, 11, and 21 being recurrent. A pathogenic HRAS mutation was identified in one case as part of the SNP array analysis. Thirteen tumors were analyzed by RNA sequencing, with 2 revealing in-frame gene fusions: TFG::GPR128 (interpreted as stochastic) and NAB2::STAT6 . The latter, originally diagnosed as JxGCT, was reclassified as SFT and excluded from the series. No fusions were detected in the remaining 11 cases; of note, no case harbored NOTCH fusions previously described in GT. Genomic methylation analysis showed that JxGCT, GT, and SFT form separate clusters, confirming that JxGCT represents a distinct entity (ie, different from GT). The results of our study show that JxGCTs are a distinct tumor type with a recurrent pattern of chromosomal imbalances that may play a role in oncogenesis, with MAPK-RAS pathway activation being likely a driver in a relatively small subset.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenomic landscape of the human dorsal root ganglion: sex differences and transcriptional regulation of nociceptive genes. Franco-Enzástiga Ãš, Inturi NN, Natarajan K, Mwirigi JM, Mazhar K, Schlachetzki JCM, Schumacher M, Price TJ
Pain (Mar 2025)

Cell states are influenced by the regulation of gene expression orchestrated by transcription factors capable of binding to accessible DNA regions. To uncover if sex differences exist in chromatin accessibility in the human dorsal root ganglion (hDRG), where nociceptive neurons innervating the body are found, we performed bulk and spatial assays for transposase-accessible chromatin technology followed by sequencing (ATAC-seq) from organ donors without a history of chronic pain. Using bulk ATAC-seq, we detected abundant sex differences in the hDRG. In women, differentially accessible regions (DARs) mapped mostly to the X chromosome, whereas in men, they mapped to autosomal genes. Hormone-responsive transcription factor binding motifs such as EGR1/3 were abundant within DARs in women, while JUN, FOS, and other activating protein 1 factor motifs were enriched in men, suggesting a higher activation state of cells compared with women. These observations were consistent with spatial ATAC-seq data. Furthermore, we validated that EGR1 expression is biased to female hDRG using RNAscope. In neurons, spatial ATAC-seq revealed higher chromatin accessibility in GABAergic, glutamatergic, and interferon-related genes in women and in Ca2+-signaling-related genes in men. Strikingly, XIST, responsible for inactivating 1 X chromosome by compacting it and maintaining at the periphery of the nucleus, was found to be highly dispersed in female neuronal nuclei. This is likely related to the higher chromatin accessibility in X in female hDRG neurons observed using both ATAC-seq approaches. We have documented baseline epigenomic sex differences in the hDRG which provide important descriptive information to test future hypotheses.]]> Wed, 31 Dec 1969 19:00:00 EST Diagnostic Use of Genome Sequencing in Patients With 11p15.5 Imprinting Disorder Features: A Pilot Study. Kessler L, Krause J, Kraft F, Amin AK, Fekete G, Lengyel A, Pinti E, Kovacs A, Lischka A, Eggermann K, Kurth I, Knopp C, Elbracht M, Begemann M, Eggermann T
Clin Genet (Mar 2025)

To assess the suitability of genome sequencing (GS) as the second step in the diagnostics of patients with the features of 11p15.5-associated imprinting disorders (ImpDis: Silver-Russell syndrome [SRS], Beckwith-Wiedemann syndrome [BWS]), we performed short-read GS in patients negatively tested for imprinting disturbances. Obtaining a genetic diagnosis for patients with the features of these syndromes is challenging due to the clinical and molecular heterogeneity and overlap, and many patients remain undiagnosed after the currently suggested stepwise diagnostic workup. GS was conducted in 48 patients (SRS features: n = 37 and BWS features: n = 11). The detection rate differed markedly between the ImpDis: although a genetic cause could be identified in 51% of patients referred with SRS features, no pathogenic variants were detected in patients with BWS features. Thus, GS substantially improves the diagnostic yield and broadens the spectrum of overlapping disorders with SRS features. Obtaining a precise molecular diagnosis provides the basis for a personalized clinical management. Our findings support the use of GS as a second-tier diagnostic tool for patients with growth disturbances, as it addresses all currently known variant types and shortens the diagnostic odyssey.]]> Wed, 31 Dec 1969 19:00:00 EST EpiMapper: A new tool for analyzing high-throughput sequencing from CUT&Tag. Dragland JS, Liu G, Nilsen HL, Böttcher Y, Wang J
Comput Biol Med (Mar 2025)

Since the invention of next-generation sequencing, new methods have been developed to understand the regulation of gene expression through epigenetic markers. Among these, CUT&Tag (Cleavage Under Targets and Tagmentation) analysis has emerged as an efficient epigenomic profiling technique with low input requirements, high sensitivity, and low background signals. Although wet-lab techniques are available, data analysis remains challenging for scientists without expert-level computational skills. Therefore, we developed EpiMapper, a new Python package that simplifies the data analysis of CUT&Tag sequencing and similar techniques, such as ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) or ChIP-seq (chromatin immunoprecipitation [ChIP] assays with sequencing), and allows biomedical scientists to easily interpret the results. This new package includes every necessary step, from quality control to annotation and differential peak analysis. In particular, EpiMapper has improved functionality (e.g., reproducibility assessment) compared to previous analysis protocols and visualization plots and provides new features, such as genome annotation and differential peak analysis. Using three case studies, two on CUT&Tag and one on ATAC-seq data, the EpiMapper Python package successfully reproduced previous results.]]> Wed, 31 Dec 1969 19:00:00 EST All the single cells: Single-cell transcriptomics/epigenomics experimental design and analysis considerations for glial biologists. Prater KE, Lin KZ
Glia (Mar 2025)

Single-cell transcriptomics, epigenomics, and other 'omics applied at single-cell resolution can significantly advance hypotheses and understanding of glial biology. Omics technologies are revealing a large and growing number of new glial cell subtypes, defined by their gene expression profile. These subtypes have significant implications for understanding glial cell function, cell-cell communications, and glia-specific changes between homeostasis and conditions such as neurological disease. For many, the training in how to analyze, interpret, and understand these large datasets has been through reading and understanding literature from other fields like biostatistics. Here, we provide a primer for glial biologists on experimental design and analysis of single-cell RNA-seq datasets. Our goal is to further the understanding of why decisions are made about datasets and to enhance biologists' ability to interpret and critique their work and the work of others. We review the steps involved in single-cell analysis with a focus on decision points and particular notes for glia. The goal of this primer is to ensure that single-cell 'omics experiments continue to advance glial biology in a rigorous and replicable way.]]> Wed, 31 Dec 1969 19:00:00 EST A menu for microbes: unraveling appetite regulation and weight dynamics through the microbiota-brain connection across the lifespan. Ribeiro G, Schellekens H, Cuesta-Marti C, Maneschy I, Ismael S, Cuevas-Sierra A, Martínez JA, Silvestre MP, Marques C, Moreira-Rosário A, Faria A, Moreno LA, Calhau C
Am J Physiol Gastrointest Liver Physiol (Mar 2025)

Appetite, as the internal drive for food intake, is often dysregulated in a broad spectrum of conditions associated with over- and under-nutrition across the lifespan. Appetite regulation is a complex, integrative process comprising psychological and behavioral events, peripheral and metabolic inputs, and central neurotransmitter and metabolic interactions. The microbiota-gut-brain axis has emerged as a critical mediator of multiple physiological processes, including energy metabolism, brain function, and behavior. Therefore, the role of the microbiota-gut-brain axis in appetite and obesity is receiving increased attention. Omics approaches such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics in appetite and weight regulation offer new opportunities for featuring obesity phenotypes. Furthermore, gut-microbiota-targeted approaches such as pre-, pro-, post-, and synbiotic, personalized nutrition, and fecal microbiota transplantation are novel avenues for precision treatments. The aim of this narrative review is ) to provide an overview of the role of the microbiota-gut-brain axis in appetite regulation across the lifespan and ) to discuss the potential of omics and gut microbiota-targeted approaches to deepen understanding of appetite regulation and obesity.]]> Wed, 31 Dec 1969 19:00:00 EST Stage-specific DNA methylation dynamics in mammalian heart development. Zhang F, Evans T
Epigenomics (Feb 2025)

Cardiac development is a precisely regulated process governed by both genetic and epigenetic mechanisms. Among these, DNA methylation is one mode of epigenetic regulation that plays a crucial role in controlling gene expression at various stages of heart development and maturation. Understanding stage-specific DNA methylation dynamics is critical for unraveling the molecular processes underlying heart development from specification of early progenitors, formation of a primitive and growing heart tube from heart fields, heart morphogenesis, organ function, and response to developmental and physiological signals. This review highlights research that has explored profiles of DNA methylation that are highly dynamic during cardiac development and maturation, exploring stage-specific roles and the key molecular players involved. By exploring recent insights into the changing methylation landscape, we aim to highlight the complex interplay between DNA methylation and stage-specific cardiac gene expression, differentiation, and maturation.]]> Wed, 31 Dec 1969 19:00:00 EST