'; ?> 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 Sun, 19 Oct 2025 18:17:46 EDT Sun, 19 Oct 2025 18:17:46 EDT jirtle@radonc.duke.edu james001@jirtle.com Methylation reference datasets from quartet DNA materials for benchmarking epigenome sequencing. Guo X, Chen Q, Zhang Y, Zhang Y, Liu Y, Duan S, Ma Y, Ni P, Wang J, He B, Ren L, Ma R, Hou W, Yu Y, Li B, Qiu F, Sun Y, Zhang Z, Xu W, Fang X, Li J, Shi L, Zhang R, Zheng Y, Dong L
Nat Commun (Oct 2025)

The lack of quantitative methylation reference datasets (ground truth) and cross-laboratory reproducibility assessment hinders clinical translation of epigenome-wide sequencing technologies. Using certified Quartet DNA reference materials, here we generate 108 epigenome-sequencing datasets across three mainstream protocols (whole-genome bisulfite sequencing, enzymatic methyl-seq, and TET-assisted pyridine borane sequencing) with triplicates per sample across laboratories. We observe strand-specific methylation biases across all protocols and libraries. Cross-laboratory reproducibility analyses reveal high quantitative methylation levels agreement (mean Pearson correlation coefficient (PCC) = 0.96) but low detection concordance (mean Jaccard index = 0.36). Using consensus voting, we construct genome-wide quantitative methylation reference datasets serving as ground truth for proficiency testing. Key technical parameters-including mean CpG depth, coverage, and strand consistency-correlate strongly with reference-dependent quality metrics (recall, PCC, and RMSE). Collectively, these resources establish foundational standards for benchmarking emerging epigenomic technologies and analytical pipelines, enabling robust, standardized quality control in research and clinical applications.]]> Wed, 31 Dec 1969 19:00:00 EST Optimized CUT&Tag enables robust epigenome profiling in Schizosaccharomyces pombe. Huang CZ, Zhou KD, Ma W
Methods (Nov 2025)

We optimized permeabilization for CUT&Tag in S. pombe, enabling robust H3K9me3 profiling using lightly fixed permeabilized sepheroplasts, overcoming limitations of ChIP-seq including crosslinking artifacts and high cell input. We established an optimized Cleavage Under Targets and Tagmentation (CUT&Tag) protocol for high-resolution epigenome profiling inSchizosaccharomyces pombeusing Critical permeabilization refinements identified Lywallzyme as the optimal enzyme for spheroplast generation (>95 % efficiency in 60 min at 10 mg/mL), outperforming Zymolyase-20 T and combinatorial treatments. Systematic parameter optimization revealed concentration-dependent digestion kinetics and an inverse cell load-efficiency relationship (5 × 10 cells achieving > 90 % conversion in 50 min at 5 mg/mL). Validated through H3K9me3 mapping in wild-type andclr4Δstrains (10⁶ cells/replicate), this approach captured specific heterochromatic enrichment at centromeres/telomeres with complete signal ablation in mutants, while reduced spike-in DNA (0.2 pg) significantly enhanced signal-to-noise ratios. The protocol enables robust epigenomic analysis with minimal cell input and enhanced resolution.]]> Wed, 31 Dec 1969 19:00:00 EST Using Epigenetic Data to Deconvolute Immune Cells in Cancer from Blood Samples. Boughanem H, Ouzounis S, Callari M, Sanz-Pamplona R, Macias-Gonzalez M, Katsila T
Methods Mol Biol (2026)

DNA methylation plays a crucial role in regulating gene expression and is a hallmark of epigenetic dysregulation in human tumors. High-throughput DNA methylation profiling can unravel intricate patterns in cancer. Moreover, understanding immune cell dynamics is essential for comprehending cancer progression and treatment response. Using DNA methylation data in immune cells, we can apply deconvolution algorithms estimate proportions of major immune cell types, providing insights into immune status and its implications in cancer. Functional analysis can identify specific overrepresented or underrepresented immune cell subsets, potentially uncovering novel biomarkers or therapeutic targets. This pipeline presents a detailed workflow in RStudio for DNA methylation studies and immune cell deconvolution, enhancing reproducibility and efficiency. The workflow integrates preprocessing, analysis, and visualization steps, facilitating robust inference of cell-type proportions from DNA methylation data.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetics in forest trees- key driver to phenotypic plasticity and adaptation under stress. Thakur S, Kumar R, Thakur L, Thakur S
Funct Integr Genomics (Oct 2025)

Forest trees are complex, long-lived organisms that have evolved to survive in their natural climates. Because of their sedentary nature, they are constantly exposed to a range of external stimuli, which might cause quick alterations in their physiological and defensive processes. Given the vital ecological role forests play in maintaining environmental equilibrium and delivering essential ecosystem services, it is critical to understand the plasticity mechanism that allow forest trees to adapt to climate change. Throughout their lives, forest trees have developed a variety of adaptation mechanisms to deal with changing environmental conditions. Among them, epigenetic changes are important regulators of plant development, growth and stress responses. The major epigenetic processes include DNA methylation, histone modifications and small RNA based chemical alterations. These mechanisms enable fast and reversible changes in gene expression by changing chromatin structure without affecting the underlying DNA sequence, allowing trees to adapt quickly to environmental signals. Importantly, some of these epigenetic alterations can be sustained over time or even passed down between generations, allowing for long-term adaptation. In this review, we highlight recent advancements in tree epigenomics, examine the epigenetic processes governing tree responses to environmental stimuli, and address their broader implications and future perspective. CLINICAL TRIAL NUMBER: Not applicable.]]> Wed, 31 Dec 1969 19:00:00 EST gene and male infertility: a South Slavic case-control study and multi-omics data integration. Kunej T, Podgrajsek R, Jaklic H, Hodzic A, Stimpfel M, Miljanovic O, Ristanovic M, Novakovic I, Plaseska-Karanfilska D, Noveski P, Ostojic S, Buretic-Tomljanovic A, Grskovic A, Peterlin B
Syst Biol Reprod Med (Dec 2025)

Components of the renin-angiotensin system (RAS) are expressed in both female and male reproductive tracts, with angiotensin I converting enzyme (ACE) being an important component for male reproductive function, as shown in animal models. The most studied polymorphism is the Alu insertion-deletion (I/D), which has been proposed to have a negative effect on male fertility. Given the conflicting evidence in the literature, we conducted a multicentric case-control study to investigate the association between the Alu I/D polymorphism and impaired spermatogenesis. Using PCR amplification and agarose electrophoresis, we genotyped the gene Alu I/D polymorphism in 745 South Slavic men. The study group consisted of 457 patients with impaired spermatogenesis, 239 with non-obstructive azoospermia (NOA) and 218 with oligoasthenoteratozoospermia (OAT) and a control group of 288 fertile men. No association was found between the Alu I/D polymorphism and these semen phenotypes, suggesting that it is not associated with NOA or severe OAT in this cohort. To provide a broader regulatory context, we also developed an integrative atlas of regulatory elements by in silico multi-omics analysis using genomics databases and bioinformatics tools. Data integration revealed various regulatory mechanisms at multiple omics levels, including genomics, epigenomics, miRNAomics, transcriptomics, proteomics and epiproteomics. These include genomic variants with predicted deleterious effects, a CpG island, microRNAs (miRNAs) and post-translational modifications (PTMs). In addition, protein interaction analysis revealed that ACE is indirectly linked to several proteins previously associated with male infertility and is also targeted by miRNA previously associated with oligozoospermia. This comprehensive, multi-faceted approach, combining genetic association analysis with bioinformatics, provides insights into regulation in its broader molecular context. These results emphasize the importance of further integrative multi-omics and systems biology research to better understand the role of ACE in male reproductive function.]]> Wed, 31 Dec 1969 19:00:00 EST Advances in single-cell DNA sequencing enable insights into human somatic mosaicism. Shao DD, Kriz AJ, Snellings DA, Zhou Z, Zhao Y, Enyenihi L, Walsh C
Nat Rev Genet (Nov 2025)

DNA sequencing from bulk or clonal human tissues has shown that genetic mosaicism is common and contributes to both cancer and non-cancerous disorders. However, single-cell resolution is required to understand the full genetic heterogeneity that exists within a tissue and the mechanisms that lead to somatic mosaicism. Single-cell DNA-sequencing technologies have traditionally trailed behind those of single-cell transcriptomics and epigenomics, largely because most applications require whole-genome amplification before costly whole-genome sequencing. Now, recent technological and computational advances are enabling the use of single-cell DNA sequencing to tackle previously intractable problems, such as delineating the genetic landscape of tissues with complex clonal patterns, of samples where cellular material is scarce and of non-cycling, postmitotic cells. Single-cell genomes are also revealing the mutational patterns that arise from biological processes or disease states, and have made it possible to track cell lineage in human tissues. These advances in our understanding of tissue biology and our ability to identify disease mechanisms will ultimately transform how disease is diagnosed and monitored.]]> Wed, 31 Dec 1969 19:00:00 EST Sex-stratified piRNA expression analysis reveals shared functional impacts of perinatal lead (Pb) exposure in murine hearts. Sala-Hamrick KE, Wang K, Perera BPU, Sartor MA, Svoboda LK, Dolinoy DC
Epigenetics (Dec 2025)

The landscape of PIWI-interacting RNA (piRNA) expression in the heart is poorly understood, particularly regarding sex differences. Altered piRNA expression has been reported in cardiovascular disease (CVD), and although exposure to the metal lead (Pb) is strongly associated with CVD risk, no studies have investigated Pb's effects on cardiac piRNAs. This study aimed to characterize piRNA expression in the murine heart and assess sex-specific effects of human-relevant maternal Pb exposure on adult offspring cardiac piRNA expression. piRNAs were identified from whole mouse hearts using sodium periodate exclusion of small RNA and subsequent sequencing. Control mice expressed 18,956 piRNAs in combined-sex analysis; sex-specific analyses revealed 9,231 piRNAs in female hearts and 5,972 piRNAs in male hearts. Genomic mapping showed 28-41% aligned to introns, while 12-28% mapped to exons. Comparing control and Pb-exposed hearts, we found more potential Pb-induced expression changes in females (847) compared to males (187) (p-value < 0.05 and |logFC| > 1). These piRNAs were significantly enriched near genes involved in biological processes related to heart function and CVD development, including mitochondrial function, energy metabolism, and cardiac muscle structure (FDR < 0.05). Overall, we characterized combined and sex-stratified piRNA expression in both control and Pb-exposed murine hearts. In addition to providing a foundation for sex-specific piRNA expression in the heart, these findings suggest a novel epigenetic mechanism by which developmental Pb exposure may impact CVD risk later in life. Future studies will link these sex-specific molecular changes to Pb-induced alterations in cardiac function.]]> Wed, 31 Dec 1969 19:00:00 EST Single-cell multi-omics in biliary tract cancers: decoding heterogeneity, microenvironment, and treatment strategies. Tang N, Li J, Gu A, Li M, Liu Y
Mol Biomed (Oct 2025)

Biliary tract cancer (BTC) is a highly heterogeneous and aggressive gastrointestinal malignancy, marked by a high mortality rate and limited treatment efficacy. The primary contributing factors include the absence of reliable early detection methods, the anatomical intricacy of the biliary system, the inherently aggressive tumor biology, and the restricted effectiveness of systemic therapies. A profound understanding of molecular characteristics and clinically relevant emerging biomarkers is essential for advancing BTC treatment strategies. Recent developments in single-cell multi-omics technologies have enabled the analysis of genetic, transcriptomic, proteomic, and metabolomic data at the single-cell resolution, thereby uncovering the heterogeneity and complexity of tumor biology. These techniques provide critical insights into the diversity of immune cell populations within the tumor microenvironment (TME) and offer novel perspectives on tumor progression and potential therapeutic interventions. While single-cell technologies have significantly advanced the study of solid tumors, their application in BTC remains nascent, with a paucity of comprehensive reviews. This review systematically integrates single-cell genomics, transcriptomics, and epigenomics data to construct a cross-omics molecular atlas of BTC. It highlights the utility of single-cell multi-omics technologies in elucidating tumor heterogeneity, microenvironment remodeling, and clonal evolution in biliary tumors, while thoroughly analyzing their implications for clinical outcomes. Furthermore, this review explores personalized treatment strategies informed by single-cell technologies and underscores the significance of these technologies as indispensable tools for unraveling the complexity of BTC and fostering mechanism-based therapeutic innovation.]]> Wed, 31 Dec 1969 19:00:00 EST and are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation. Daskeviciute D, Sainty B, Chappell-Maor L, Bone C, Russell S, Iglesias-Platas I, Arnaud P, Monteagudo-Sánchez A, Greenberg MVC, Chen K, Manerao-Azua A, Perez de Nanclares G, Lartey J, Monk D
Epigenetics (Dec 2025)

Genomic imprinting is the parent-of-origin specific monoallelic expression of genes that result from complex epigenetic interactions. It is often achieved by monoallelic 5-methylcytosine, resulting in the formation of differentially methylated regions (DMRs). These show a bias towards oocyte-derived methylation and survive reprogramming in the pre-implantation embryo. Imprinting is widespread in the human placenta. We have recently performed whole-genome screens for novel imprinted placenta-specific germline DMRs (gDMRs) by comparing methylomes of gametes, blastocysts and various somatic tissues, including placenta. We observe that, unlike conventional imprinting, for which methylation at gDMRs is observed in all tissues, placenta-specific imprinting is associated with transient gDMRs, present only in the pre-implantation embryo and extra-embryonic lineages. To expand the list of imprinted genes subject to placenta-specific imprinting, we reinvestigated our list of candidate loci and characterized two novel imprinted genes, and , both of which display polymorphic imprinting. Interrogation of placenta single-cell RNA-seq datasets, as well as cell-type methylation profiles, revealed complex cell-type specificity. We further interrogated their methylation and expression in placental samples from complicated pregnancies, but failed to identify differences between intrauterine growth restricted or pre-eclamptic samples and controls, suggesting they are not involved in these conditions.]]> Wed, 31 Dec 1969 19:00:00 EST Immunofluorescence Staining and Microscopic Imaging of Plant Nuclei for Epigenetic Modifications. Gandhivel VH, Raju S, Shivaprasad PV
Methods Mol Biol (2026)

Histone posttranslational modifications (PTMs) and DNA methylation are the predominant epigenetic modifications on the chromatin that regulate gene expression. These modifications can be spatially resolved using microscopic examination of the nuclei with the help of commercially available antibodies. Here, we describe a detailed method to obtain intact nuclei from plant tissues and reproducibly immunostain the nuclei for specific chromatin marks and microscopic examination. This method can be readily extended to multiple plant species as the antibodies are raised against conserved epigenetic marks.]]> Wed, 31 Dec 1969 19:00:00 EST The myoblast methylome: multiple types of associations with chromatin and transcription. Sen S, Lacey M, Baribault C, Ponnaluri VKC, Esteve PO, Ehrlich KC, Meletta M, Pradhan S, Ehrlich M
Epigenetics (Dec 2025)

Epigenetic changes are implicated in development, repair, and physiology of postnatal skeletal muscle (SkM). We generated methylomes for human myoblasts (SkM progenitor cells) and determined myoblast differentially methylated regions (DMRs) for comparison to the epigenomics and transcriptomics of diverse cell types. Analyses were from global genomic and single-gene perspectives and included reporter gene assays. One atypical finding was the association of promoter-adjacent hypermethylation in myoblasts with transcription turn-on, but at downmodulated levels, for certain genes (., and ). In contrast, brain-specific was in repressed chromatin and silent in most cell types but linked to hypermethylated DMRs specifically in myoblasts. The -linked DMRs might be needed because of the overlapping or nearby binding of myogenic differentiation protein 1 (MYOD). We found genome-wide overlap of DMRs with MYOD or CCCTC-binding factor (CTCF) binding sites in myoblasts that is consistent with the importance of MYOD, as well as CTCF, in organizing myoblast transcription-enhancing chromatin interactions. We also observed some gene upregulation correlated with a special association of regional DNA hypomethylation with H3K36me3, H3K27ac, and H3K4me1 enrichment. Our study highlights unusual relationships between epigenetics and gene expression that illustrate the interplay between DNA methylation and chromatin epigenetics in the regulation of transcription.]]> Wed, 31 Dec 1969 19:00:00 EST Perfluoroalkyl substance pollutants disrupt microglia function and trigger transcriptional and epigenomic changes. Cheng Y, Li JR, Yu H, Li S, Tychhon B, Cheng C, Weng YL
Toxicology (Nov 2025)

Per- and polyfluoroalkyl substances (PFAS), commonly referred to as "forever chemicals", are widely utilized in various industries and consumer products worldwide. Their exposure has been associated with numerous diseases and malignancies, including neurodevelopmental and neurodegenerative disorders. However, the molecular mechanisms underlying PFAS-induced adverse effects on the central nervous system (CNS) remain poorly understood. In this study, we investigated the transcriptomic and epigenetic changes in microglia exposed to perfluorooctane sulfonate (PFOS), a prevalent PFAS compound. Our findings demonstrate that 24-hour PFOS exposure (25 and 50 µM) disrupts the microglial transcriptome and compromises their homeostatic state, marked by increased inflammation and impaired actin cytoskeleton remodeling. Comparative analysis with in vivo transcriptional states revealed that PFOS-exposed microglia exhibit gene expression profiles resembling those of aged microglia. Additionally, profiling of active chromatin regions uncovered significant alterations in the H3K27ac landscape in PFOS-exposed microglia. Notably, these epigenetic disruptions persisted even after PFOS withdrawal, with a subset of H3K27ac-enriched regions remaining altered, suggesting the presence of lasting epigenetic scars. Furthermore, transcription factor analysis implicated the AP-1 and TEAD families as potential upstream regulators connecting the altered chromatin landscape to transcriptomic changes. Collectively, these findings provide mechanistic insights into how PFOS exposure disrupts microglial function and highlight its potential role in exacerbating neurodegenerative processes.]]> Wed, 31 Dec 1969 19:00:00 EST Differential methylation patterns in cord blood associated with prenatal exposure to neighborhood crime: an epigenome-wide association study and regional analysis. Martin CL, Chen J, D'Alessio AS, Ward-Caviness CK, Ye A, Lodge EK, Ghastine L, Dhingra R, Jima DD, Murphy SK, Hoyo C
Epigenetics (Dec 2025)

Exposure to prenatal social stressors during pregnancy is associated with adverse birth outcomes and has been linked to epigenetic changes in DNA methylation (DNAm); however, less understood is the effect of neighborhood-level stressors like crime during pregnancy on offspring DNAm. Using data from the Newborn Epigenetic Study, we conducted epigenome-wide and regional analyses of the association between exposure to neighborhood crime and DNAm in offspring cord blood using Illumina's HumanMethylation450k BeadChip among 185 mother-offspring pairs. Prenatal exposure to neighborhood crime at the census block group level was mapped to participants' residential addresses during the gestational window from the date of last menstrual period to delivery. Models for the epigenome-wide and regional analyses were adjusted for maternal age, race/ethnicity, education, smoking, cell-type composition, and offspring sex. Genetic influence and gene expression enrichment were assessed using methylation quantitative trait loci (mQTLs) and expression quantitative trait methylation (eQTMs) analyses. Functional enrichment was determined using Gene Ontology and KEGG databases. We did not find evidence of epigenome-wide associations between prenatal neighborhood crime exposure and DNAm; however, we identified nine differentially methylated regions (DMRs) comprising 51 CpG sites associated with neighborhood crime. CpG sites within significant differentially methylated regions were associated with mQTLs at birth and eQTMs upon further examination. KEGG analysis identified a significant Th1 and Th2 cell differentiation pathway. Our results suggest potential links between prenatal neighborhood crime exposure and offspring DNAm; however, additional research is needed in larger cohorts across wider geographic areas to confirm our results.]]> Wed, 31 Dec 1969 19:00:00 EST New frontiers in O-MFS: omic-maxillofacial surgery toward a translational approach to patient care. Monarchi G, Gobbo M, Guarda Nardini L
Eur Arch Otorhinolaryngol (Oct 2025)

The integration of omics sciences into maxillofacial surgery marks a transformative step toward a new model of personalized and translational patient care. Recent advances in genomics, transcriptomics, and epigenomics are reshaping the understanding and management of head and neck squamous cell carcinoma (HNSCC), one of the most challenging malignancies in the maxillofacial region due to its biological heterogeneity and poor prognosis. Omics sciences offer unprecedented insight into the molecular landscape of these tumors, allowing the identification of specific biomarkers that predict patient outcomes and guide tailored surgical strategies. A landmark study by Ribeiro et al. demonstrated the clinical value of a nine-gene multi-omics signature capable of distinguishing HNSCC patients with markedly different survival rates, independent of metastasis status. This signature integrates copy number alterations, gene expression profiles, and methylation patterns linked to key cellular processes such as DNA repair, cytoskeletal dynamics, and immune response. The concept of "Omic-Maxillofacial Surgery" (O-MFS) envisions a future where molecular data complement anatomical, pathological, and functional criteria to refine surgical planning, intraoperative decision-making, and postoperative surveillance. Despite challenges related to data complexity, clinical validation, and cost, this emerging approach promises to revolutionize maxillofacial oncology by enabling more accurate patient stratification and truly personalized surgical care.]]> Wed, 31 Dec 1969 19:00:00 EST use capsules, transporters, mobile genetic elements, and other evolutionary adaptations to survive antibiotics exposure in the absence of resistance genes. Mmatli M, Mbelle NM, Fourie B, Osei Sekyere J
Virulence (Dec 2025)

Whole-genome sequencing, transcriptomic profiling, and epigenomic analyses were performed. Phenotypic assays were used to evaluate the effects of various inhibitors on antibiotic susceptibility, while bioinformatic pipelines were used to characterize resistance determinants, virulence factors, and mobile genetic elements (MGEs).]]> Wed, 31 Dec 1969 19:00:00 EST Interrogating Metabolic Plasticity in Marine Organisms: A Framework for Best Practices Using Metabolomic and Lipidomic Approaches. Venkataraman YR, Huffmyer AS
Integr Comp Biol (Oct 2025)

Understanding the mechanisms that underlie resilience in marine invertebrates is critical as climate change and human impacts transform coastal ecosystems. Metabolic plasticity, or an organism's capacity to modulate energy production, allocation, and use, plays a central role in mediating resilience under environmental stress. While research on marine invertebrate stress responses has grown, integrative studies that examine metabolic plasticity by connecting molecular, physiological, and organismal scales remain limited. In this Perspective, we advocate for the rigorous and thoughtful use of metabolomic and lipidomic approaches to understand resilience in marine systems through the lens of metabolic plasticity. We provide recommendations for experimental design, summarize current methodologies, and provide an overview of commonly used data analysis approaches. Advances in other molecular approaches such as genomics, epigenomics, and transcriptomics can be harnessed to further explore stress responses through multi-omic integrative analyses. As quantitative integrative analysis remains limited in marine fields, we call for a stronger integration of molecular, metabolomic, physiological, and organismal data sets to link mechanisms to phenotypes. We explore the use of these approaches in studies of marine invertebrates and highlight promising areas of multi-omic research that deserve exploration. By embracing metabolic complexity and scaling from molecules to phenotypes, we suggest that the marine invertebrate research community will be better equipped to understand, anticipate, and mitigate the impacts of environmental change on marine ecosystems.]]> 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 Unlocking the metabolic potential of endophytic fungi through epigenetics: a paradigm shift for natural product discovery and plant-microbe interactions. Liu R, Peng XP, Newman DJ, Purchase D, Li G, Kusari S
Nat Prod Rep (Oct 2025)

Covering: up to December 2024Microbial metabolic pathways, including those of endophytic fungi, offer significant potential for synthesizing secondary metabolites, regardless of their ecological niche. These pathways can be modulated at the molecular level through genome and epigenome manipulation. The metabolic activation of fungal endophytes using epigenetics presents an exciting frontier in science, paving the way for advanced biotechnological applications and enhancing our understanding of these microorganisms' roles in ecosystems. This review examines the significant role of epigenetics in the biosynthesis of secondary metabolites from fungal endophytes, which is vital for drug discovery. Our primary focus centers on studies that explore the epigenetic modulation of endophytic fungi up until December 2024. Acknowledging the rapidly evolving landscape of epigenetic research in this field, which has limited examples for endophytic fungi, we provide crucial foundational insights into fungal epigenetics and relate these insights to the broader context of plant-microbe interactions and endophytic fungal epigenetics, supported by relevant examples. Key mechanisms, such as histone acetylation, histone methylation, and DNA methylation, are discussed alongside recent advances in small-molecule epigenetic modulators that can activate silent biosynthetic gene clusters (BGCs). Further, chromatin-dependent regulation of these BGCs and methods for probing chromatin modifications and secondary metabolism in fungi are discussed. The role of CRISPR-Cas9 genome editing, combined with epigenetic strategies, is highlighted, showcasing its ability to alter the metabolite profiles of fungal endophytes. Finally, we explore how artificial intelligence (AI), machine learning (ML), and deep learning (DL) innovations are transforming research in chemical epigenomics at the plant-microbe interface.]]> Wed, 31 Dec 1969 19:00:00 EST Biomarkers to predict, prevent, and treat persistent pain: omics. Hutchinson MR, Barratt D, Johnston CH, Humphries MA, Semmler C, Tettamanzi GC, Greentree AD, Rolan P
Pain (Nov 2025)

Persistent pain represents a significant global health challenge, necessitating innovative biomarker technologies that facilitate personalised prediction, prevention, and treatment. Recent advances in omics, encompassing genomics, proteomics, transcriptomics, lipidomics, epigenomics, and metabolomics, now permit high-resolution mapping of neuroimmune pathways implicated in pain chronification. Yet, biomarkers must transcend isolated molecular or sensory indicators, integrating emotional, cognitive, functional, and social dimensions of pain. Emerging quantum sensing technologies, such as diamond nitrogen-vacancy sensors and portable magnetoencephalography systems, promise precise and wearable tools capable of real-time, multimodal assessment of pain. Concurrently, transparent machine learning methods combining explainable artificial intelligence with physiologically informed modelling are crucial for managing the vast data complexity inherent to these multidimensional omics approaches. Ultimately, achieving economically viable, environmentally sustainable, and universally accessible pain management solutions requires strategically streamlined methods. Here, we outline a visionary framework of measurement-enabled understanding that enables precision pain medicine with rapid feedback that points toward actionable clinical outcomes, harnessing interdisciplinary innovation to address persistent pain comprehensively, just as genomics and immunotherapy have transformed cancer care.]]> Wed, 31 Dec 1969 19:00:00 EST Brain DNA Methylation Atlas of App Alzheimer's Disease Model Mice Across Age and Region Reveals Choline-Induced Resilience. Krunic A, Bellio TA, Cohen BZ, Labadorf A, Stein TD, Lin H, Mellott TJ, Blusztajn JK
Aging Cell (Oct 2025)

Alzheimer's disease (AD) is the most common type of dementia. Current treatments for AD are inadequate, and there is a need to design preventive strategies that would improve the resistance or resilience to AD pathology. Because aberrant brain DNA methylation (DNAm) is associated with hallmarks of AD, we tested the hypothesis that a nutritional approach using choline, an essential nutrient and methyl donor, would modulate DNAm to ameliorate AD pathologies. Previous studies showed that perinatal choline supplementation (PCS) reduced AD-like neuropathology and inflammation while improving cognitive performance in AD mouse models. Here we investigated hippocampal and cerebral cortical DNAm patterns by reduced representation bisulfite sequencing from 3 to 12 months in wild-type (WT) and App AD model mice fed a 1.1 g/kg control or 5.5 g/kg PCS diet from conception to weaning. App mice showed extensive CpG DNAm changes, which were associated with the age-dependent progression of amyloidosis. PCS induced genotype-specific DNAm patterns and reversed DNAm changes in multiple genes in App mice. By associating DNAm with matched transcriptomics, we found that DNAm in App mice correlated with the expression of microglial genes, while DNAm-associated genes modulated by PCS were related to synaptic function. Moreover, we found that methylation levels of several CpGs were associated with levels of beta amyloidosis, relating epigenetic changes to neuropathology. Overall, our data suggest that DNAm in the brain serves as an epigenetic mechanism for abnormal gene expression in App mice and indicate that PCS may promote resilience to synaptic dysfunction through modulating DNAm.]]> Wed, 31 Dec 1969 19:00:00 EST