'; ?> 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 Sat, 14 Mar 2026 07:13:45 EDT Sat, 14 Mar 2026 07:13:45 EDT jirtle@radonc.duke.edu james001@jirtle.com Multi-omics biomarker detection in smoking induced COPD. Syed RU, Khaled Bin Break M, Akasha R, Elafandy NM, Abobaker SH, Khalifa AAS, Aboshouk NAM, Nashmi Alghaythi A, Altwalah LA, Menwer Aldhafeeri RM, Khan MSA, Gupta G
Clin Chim Acta (Mar 2026)

Chronic obstructive pulmonary disease (COPD) is marked by heterogeneity, and traditional spirometric biomarkers fall short of fully capturing its underlying molecular complexity. This review discusses recent developments in multi-omics profiling, such as transcriptomics, proteomics, metabolomics, and epigenomics/acetylomics, to define biologically meaningful COPD endotypes and enhance their clinical categorization. Reproducible circulating protein markers identified in proteomic studies include surfactant protein D (SP-D), club cell secretory protein (CC16), fibrinogen, and inflammatory cytokines, which predict disease severity, risk of exacerbation, and mortality. Further evidence of dysregulated histone/protein acetylation and other post-translational modifications in chronic inflammation, steroid resistance, and disease progression is provided by epigenomic studies (such as DNA methylation, non-coding RNAs, and chromatin remodeling) and acetylomic analyses. Notably, integrative multi-omics solutions exhibit better outcomes than single-biomarker solutions by allowing the identification of molecular endotypes that are more likely to accommodate clinical heterogeneity. Nevertheless, it is significantly constrained by cohort and platform heterogeneity, including factors such as smoking exposure, age, comorbidities, treatment, and sample processing methods. Overall, the existing evidence highlights the importance of multi-omics integration in the further development of precision diagnostics and individualized management of COPD, bridging the gap between molecular pathology and clinical decision-making.]]> Wed, 31 Dec 1969 19:00:00 EST : a computational suite for DNA methylation sequencing data analysis. Loyfer N, Rosenski J, Kaplan T
Life Sci Alliance (Apr 2026)

Next-generation methylation-aware sequencing of DNA sheds light on the fundamental role of methylation in cellular function in health and disease, increasing the number of covered CpG sites from hundreds of thousands in previous array-based approaches to tens of millions across the whole genome. While array-based approaches are limited to single-CpG resolution, next-generation sequencing allows for a more detailed, single-molecule fragment-level analysis; however, existing tools to fully use this capability are not yet well developed. Here, we present , an extensive computational suite tailored for methylation sequencing data. allows fast access and ultracompact anonymized representation of high-throughput methylome data, obtained through various library preparation and sequencing methods, with a custom epiread file format achieving a compression factor of over 100x from the input BAM file. In addition, contains state-of-the-art algorithms for genomic segmentation, biomarker identification, genetic and epigenetic data integration, and more. offers fragment-level analysis and informative visualizations, across multiple genomic regions and samples.]]> Wed, 31 Dec 1969 19:00:00 EST Melatonin-enabled omics: understanding plant responses to single and combined abiotic stresses for climate-smart agriculture. Raza A, Li Y, Charagh S, Guo C, Zhao M, Hu Z
GM Crops Food (Dec 2026)

Climate change-driven single and combined abiotic stresses pose escalating threats to sustainable, climate-smart agriculture and global food security. Melatonin (MLT, a powerful plant biostimulant) has established noteworthy potential in improving stress tolerance by regulating diverse physiological, biochemical, and molecular responses. Therefore, this review delivers a comprehensive synopsis of MLT-enabled omics responses across genomics, transcriptomics, proteomics, metabolomics, miRNAomics, epigenomics, phenomics, ionomics, and microbiomics levels that collectively regulate plant adaptation to multiple abiotic stresses. We also highlight the crosstalk between these omics layers and the power of integrated multi-omics (panomics) approaches to harness the complex regulatory networks underlying MLT-enabled stress tolerance. Lastly, we argue for translating these omics insights into actionable strategies through advanced genetic engineering and synthetic biology platforms to develop MLT-enabled, stress-smart crop plants.]]> Wed, 31 Dec 1969 19:00:00 EST Ontology-aware DNA methylation classification with a curated atlas of human tissues and cell types. Kim M, Dannenfelser R, Cui Y, Allen G, Yao V
Cell Rep Methods (Mar 2026)

DNA methylation is a key regulatory mechanism reflecting both short- and long-term biological stimuli. While it has been widely used to study aging through disease-associated methylation shifts, its potential for revealing tissue-specific shifts remains underexplored due to the lack of comprehensive reference atlases with correspondingly systematic analysis framework. To address this, we assemble the largest and most diverse atlas of healthy human tissue and cells profiled by 450K arrays, totaling 16,959 samples across 86 tissues and cell types. Using this resource, we introduce an ontology-aware classification framework that identifies robust CpG features linked to tissue and cell identity and incorporates known anatomical and functional relationships. Through minipatch learning, we distill 190 CpGs that support accurate multilabel classification and validate the approach with ontology-based label transfer to 31 unseen tissue and cell types.]]> Wed, 31 Dec 1969 19:00:00 EST A cell type enrichment analysis tool for brain DNA methylation data (CEAM). Müller J, Laroche VT, Imm J, Weymouth L, Harvey J, Reijnders RA, Smith AR, van den Hove D, Lunnon K, Cavill R, Pishva E
Epigenetics (Dec 2026)

DNA methylation (DNAm) signatures are highly cell type-specific, yet most epigenome-wide association studies (EWAS) are performed on bulk tissue, potentially obscuring critical cell type-specific patterns. Existing computational tools for detecting cell type-specific DNAm changes are often limited by the accuracy of cell type deconvolution algorithms. Here, we introduce CEAM (Cell-type Enrichment Analysis for Methylation), a robust and interpretable framework for cell type enrichment analysis in DNA methylation data. CEAM applies over-representation analysis with cell type-specific CpG panels from Illumina EPIC arrays derived from nuclei-sorted cortical post-mortem brains from neurologically healthy aged individuals. The constructed CpG panels were systematically evaluated using both simulated datasets and published EWAS results from Alzheimer's disease, Lewy body disease, and multiple sclerosis. CEAM demonstrated resilience to shifts in cell type composition, a common confounder in EWAS, and remained robust across a wide range of differentially methylated positions, when upstream modeling of cell type composition was modeled with sufficient accuracy. Application to existing EWAS findings generated in neurodegenerative diseases revealed enrichment patterns concordant with established disease biology, confirming CEAM's biological relevance. The workflow is publicly available as an interactive Shiny app (https://um-dementia-systems-biology.shinyapps.io/CEAM/) enabling rapid, interpretable analysis of cell type-specific DNAm changes from bulk EWAS.]]> Wed, 31 Dec 1969 19:00:00 EST Portrait of a Spectrum: Clinical and Genetic Characterization of a Large Cohort of Chromatinopathies-30 Years' Experience From a Third Level Center. Marchetti GB, Rosina E, Meossi C, Mura M, Pezzani L, Selicorni A, Bedeschi MF, Tenconi R, Agostoni C, Finelli P, De Matteis S, Di Fede E, Massa V, Pezzoli L, Gervasini C, Iascone M, Milani D
Clin Genet (Apr 2026)

Chromatinopathies (CPs) are an expanding group of rare genetic disorders affecting epigenetic machinery. Besides an intricate genotypic spectrum, these conditions share overlapping phenotypes characterized by neurocognitive impairment, growth defects and distinctive, but often convergent, facial features. Although individually rare, the landscape of CPs is increasingly growing and represents an emerging and possibly underestimated cause of disability. Due to their complexity and rarity, accurate diagnosis and management pose significant difficulties. To address these challenges and gain a deeper overview of these diseases' spectrum, we retrospectively collected clinical characteristics of 239 patients diagnosed with CPs and critically analyzed their diagnostic journey, growth charts, neurological and gestaltic features. Starting from the largest collection of CPs to date, our data point to wide sequencing analyses as the best shortcut to diagnosis. We have also demonstrated the importance of growth defects in this group of disorders that require dedicated growth tables, and we have delved into the great variability of neurological and clinical burden in these conditions. This retrospective study provides a significant advance in our understanding of these rare diseases and will help to improve diagnostic, therapeutic, and clinical approaches to CPs and to develop personalized multidisciplinary care plans for affected patients.]]> Wed, 31 Dec 1969 19:00:00 EST Long noncoding RNA H19 in liver development and disease. Montoya-Durango DE, Gobejishvili L
Cell Signal (Jun 2026)

Liver disease is a global health problem responsible for more than two million deaths annually. Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) are major contributors to chronic liver disease-related morbidity and mortality. Factors like diet and alcohol consumption have become key drivers of liver pathologies including steatosis, fibrosis/cirrhosis, and hepatocellular carcinoma. To date very few treatments are available, hence there is a critical need for the development of novel therapies to slow down the development/progression of liver damage. The long non-coding RNA H19 gene, H19, is an imprinted gene normally expressed from the maternally inherited chromosome and epigenetically silenced in the paternal chromosome. At the embryo stage H19 controls genome-wide methylation, directs the methylation of the imprinted gene network, and regulates organ size. In the livers of neonates, H19 is important for organ maturation but remains silent in the mature organ. H19 re-expression in the adult liver drives de novo lipogenesis and fibrosis and maintains a proliferative state in tumor cells. The complexity of H19 functions in the liver is reflected in its interaction and regulation of a growing number of proteins, and coding and non-coding RNAs involved in metabolism, pro-fibrotic gene networks, cell cycle progression, and chromatin regulation. This review summarizes the findings related to the role of H19 in liver development and in diseases such as fatty liver, fibrosis, and hepatocellular carcinoma.]]> Wed, 31 Dec 1969 19:00:00 EST Accessing crop genetic diversity via pangenomics. MacNish TR, Kopalli V, Zanini SF, Snowdon RJ, Golicz AA, Edwards D
Theor Appl Genet (Mar 2026)

With the increasing accuracy and decreasing cost of sequencing technology, the extent of structural variation (SV) and its importance in crop species has become increasingly evident. SVs such as insertions, deletions, and inversions have been associated with genetic variation of agronomically important traits and the diversification of crop species. Pangenomes aim to capture the genetic diversity of a species, population or genus, by incorporating the genomes of multiple individuals. The additional genetic diversity represented by a pangenome compared to a single-genome reference can aid the association of variation with traits and support crop improvement. Genus-wide pangenomes representing related crop species as well as their wild relatives can be used to identify and introduce novel genetic variation associated with agronomically important traits into crops. Pangenomes can aid crop improvement through pangenome assisted breeding (PAB) and genome editing. PAB is an adaption of marker assisted breeding that associates pangenome-based markers, including single nucleotide polymorphisms (SNPs) and SVs, with a trait of interest. Genome editing can use CRISPR/cas9 or similar tools to introduce or change the expression of agronomically important SVs. Pan-epigenomics is an emerging field that can complement pangenomics studies by identifying epigenetic modifications such as DNA methylation, histone modifications, and chromatin accessibility, which play important roles in regulating gene expression and have been shown to contribute to intraspecific diversity and agronomically important traits. We highlight the advances of crop pangenomics and their use in crop breeding and improvement.]]> Wed, 31 Dec 1969 19:00:00 EST Introduction to the special issue on epigenetic regulation of chronic pain. Nackley AG
Pain Rep (Apr 2026)

This Special Issue features 6 articles from leaders in the field that elucidate novel epigenetic mechanisms regulating nociception, inflammation, responses to pharmacologic and integrative therapies, and pain disparities among racial/ethnic groups. Together, they highlight the expanding potential of epigenomics to inform mechanistic discovery, guide personalized pain therapeutics, and advance pain equity.]]> Wed, 31 Dec 1969 19:00:00 EST Interactions between nutrition and the epigenome: how can it be harnessed for public health? Anastasopoulou M, Dereki I, Sgourou A, Lagoumintzis G
Future Sci OA (Dec 2026)

A substantial body of evidence shows that dietary habits influence gene expression and epigenetic processes, holding significant implications for public health policies. Epigenetic modifications are increasingly associated with metabolic state, disease risk, and biological aging. Translating mechanistic results into scalable, efficient nutritional epigenetics treatments is difficult.]]> Wed, 31 Dec 1969 19:00:00 EST Hyperglycaemia-induced metabolic stress and epigenetic imprinting in the inflammatory pathogenesis of diabetic neuropathy. Razi FB, Ashraf H, Singhal S, Qamar Z, Moin S
Diabetes Res Clin Pract (Apr 2026)

Diabetic neuropathy (DN), a major microvascular complication of diabetes mellitus, results from a complex interplay among oxidative stress, inflammation, and persistent epigenetic modifications. Hyperglycemia-induced mitochondrial dysfunction increases reactive oxygen species (ROS), which activate redox-sensitive inflammatory cascades, including NF-κB, JAK/STAT, and the NLRP3 inflammasome. These pathways amplify cytokine release and neuronal sensitisation, while reciprocal feedback between ROS and inflammation mediated by Nrf2 suppression further perpetuates nerve damage. Damage-associated molecular patterns (DAMPs), including HMGB1, S100A8/A9, mitochondrial DNA, and extracellular ATP, act as key amplifiers of neuroinflammation. By engaging receptors such as RAGE, Toll-like receptors (TLRs), and NOD-like receptors (NLRs), particularly NLRP3, these DAMPs trigger glial activation and nociceptive signalling, contributing to axonal degeneration and pain hypersensitivity in DN. Epigenetic dysregulation, including DNA methylation drift, histone modification imbalance, and aberrant non-coding RNA expression, constitutes a critical mechanism underlying metabolic memory, wherein prior hyperglycemic exposure leaves lasting molecular imprints. Persistent histone acetylation (H3K9ac), altered methylation (H3K4me1/Set7, H3K9me3/SUV39H1), and stable 5-methylcytosine patterns sustain inflammatory and oxidative pathways, even after glucose normalisation. Therapeutically, DNMT and HDAC inhibitors, miRNA modulators, and agents targeting RAGE/TLR4/NLRP3 pathways show promise in reversing these molecular imprints. Antioxidants and anti-inflammatory compounds with epigenetic effects further represent potential disease-modifying strategies. Future research must focus on longitudinal human studies, nerve-specific epigenomics, and multi-omics integration to enable personalised, mechanism-based therapy for DN. Understanding the interdependence of ROS, DAMPs, and epigenetic memory is key to breaking the cycle of chronic neuroinflammation and neuronal injury.]]> Wed, 31 Dec 1969 19:00:00 EST Synergistic integration of clinical and multi-omics data for early MCI diagnosis using an attention-based graph fusion network. Yu S, Zhao J, Ouyang J, Wang X, Kou P, Zhu K, Liu P
J Neurosci Methods (Apr 2026)

Mild cognitive impairment (MCI), a precursor to Alzheimer's disease (AD), requires precise early diagnosis. Single-omics approaches often miss disease complexity, motivating integrative and interpretable solutions.]]> Wed, 31 Dec 1969 19:00:00 EST Multi-omics biomarkers in psychiatric disorders diagnosis and stratification. Khatami SH, Anoosheh S, Khodaparast M, Maghsoudloonejad A, Dadgostar E, Asadi A, Kaveh M, Haghighi MM
Clin Chim Acta (Apr 2026)

The precise diagnosis and stratification of psychiatric disorders remain formidable challenges in modern medicine, hindered by the absence of objective biomarkers and reliance on subjective clinical criteria. Recent advances in multi-omics technologies, including genomics, transcriptomics, proteomics, metabolomics, and epigenomics, have revolutionized our understanding of complex neuropsychiatric conditions such as schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder. This review critically evaluates the current landscape of multi-omics research in psychiatry, highlighting methodological innovations, integrative strategies, and translational potential for biomarker discovery and clinical implementation. By synthesizing data across diverse molecular layers, multi-omics approaches enable a systems-level view of psychiatric disorders as multifactorial entities shaped by molecular, cellular, environmental, and neurocircuitry interactions. Despite promising advances in diagnostic accuracy and personalized treatment, significant barriers persist, including data heterogeneity, analytical complexity, and the translational gap between molecular signatures and clinical phenotypes. This review systematically explores the contributions of individual omics domains, emerging frameworks for multimodal data integration, the role of systems biology and network-based models, and the impact of large-scale consortia in driving clinical translation.]]> Wed, 31 Dec 1969 19:00:00 EST EnsembleAge: enhancing epigenetic age assessment with a multi-clock framework. Haghani A, Lu AT, Yan Q, Belmonte JCI, Reddy P, Cheng V, Yang XW, Wang N, Mozhui K, Murach K, Ocampo A, Williams RW, Jucker M, Bergmann C, Poganik JR, Zhang B, Gladyshev VN, Horvath S
Geroscience (Apr 2026)

Several widely used epigenetic clocks have been developed for mice and other species, but a persistent challenge remains: different mouse clocks often yield inconsistent results. To address this limitation in robustness, we present EnsembleAge, a suite of ensemble-based epigenetic clocks. Leveraging data from over 200 perturbation experiments across multiple tissues, EnsembleAge integrates predictions from multiple penalized models. Empirical evaluations demonstrate that EnsembleAge outperforms existing clocks in detecting both pro-aging and rejuvenating interventions. Furthermore, we introduce EnsembleAge HumanMouse, an extension that enables cross-species analyses, facilitating translational research between mouse models and human studies. Together, these advances underscore the potential of EnsembleAge as a robust tool for identifying and validating interventions that modulate biological aging.]]> Wed, 31 Dec 1969 19:00:00 EST Rising Star: Single Cell Omics Technologies: When Whole Omics Analysis Meets Single Cell Resolution. Tang F
J Mol Biol (Apr 2026)

I got my PhD degree under the supervision of Prof. Kegang Shang in 2003. And I did my postdoc research in Azim Surani's lab. Then I set up my own lab in Biomedical Pioneering Innovation Center at Peking University in 2010. My research has focused on developing single-cell omics sequencing technologies and employing these powerful tools to dissect the gene regulation networks in human germline cell development under both physiological and pathological conditions. My lab systematically developed a serial of single-cell omics sequencing technologies, including the first single-cell DNA methylome sequencing technology in 2013, which was considered to pioneer the single-cell epigenome field. In recent years, my lab has focused on developing single-cell omics long-read sequencing technologies based on single-molecule sequencing platforms, which can reveal critical features of the repetitive elements. The repetitive elements are considered as 'dark matter', which account for over half of our genome and play important roles for both normal development and numerous diseases. The research in my lab revealed critical features of the epigenetic reprogramming of human germline cells, deepening our understanding of these cells, which are fundamental to the transgenerational immortality of the human species.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic Age Acceleration and Mortality Among Persons with Poorly Controlled HIV. Sosnowski DW, Shu C, Hsu HY, Jiang Y, Kathuria A, Piggott DA, Mehta SH, Kirk GD, Maher BS, Sun J
J Gerontol A Biol Sci Med Sci (Mar 2026)

We sought to assess the relationship between HIV infection and disease severity with epigenetic age and to examine the combined association of epigenetic age acceleration and HIV infection with mortality. Participants were drawn from the ALIVE study, a community-based cohort of persons who inject drugs (PWID) in Baltimore, USA. DNA from buffy coat samples was bisulfite-treated and assayed using the Illumina MethylationEPIC BeadChip. Repeated assessment of epigenetic age was indexed using PhenoAge, Horvath age, Hannum age, GrimAge, and DunedinPACE of aging. Annual linkage to the National Death Index-Plus provided mortality data. Linear mixed-effects regressions compared epigenetic age acceleration trajectories. Cox models estimated hazard ratios for all-cause mortality by epigenetic age and HIV status, adjusting for demographics, risk behaviors, cell compositions, and ancestry principal components. Among 396 participants (127 with HIV [PWH]) and 3,862 person-years of follow-up, the median baseline age was 48.5 years; 89% were Black and 69% male. PWH showed greater epigenetic age acceleration than people without HIV (PWoH), especially those with detectable viremia, low CD4 counts, and low CD4: CD8 ratios. Both HIV and epigenetic age acceleration were independently associated with all-cause mortality. Compared to PWoH without PhenoAge acceleration, PhenoAge acceleration with or without HIV was associated with 3.28 (95% CI: 2.06, 5.02) and 2.12 (95% CI: 1.32, 3.41) times higher mortality hazard, respectively. HIV infection, uncontrolled viremia, and poor immune recovery are linked to epigenetic age acceleration, contributing to mortality risk among PWID, underscoring the need to address molecular aging to mitigate mortality in this population.]]> Wed, 31 Dec 1969 19:00:00 EST DNA methylation-mediated alterations in Copper(I/II) redox equilibrium underlie lead-induced neurotoxicity. Hu J, Wang WX
Environ Pollut (Apr 2026)

Lead (Pb), a ubiquitous environmental toxin, poses significant risks to central nervous system health, primarily by disrupting essential metal homeostasis in the brain. While epigenetic regulation and proteomic expression are significantly affected by Pb, its specific molecular impact on copper (Cu) redox states remains poorly understood. This study systematically investigated the molecular mechanisms underlying Pb-induced neurotoxicity in SH-SY5Y cells through integrated epigenomics and proteomics analysis. DNA methylation analysis revealed 141,357 differentially methylated regions (DMRs), primarily in CpG sites, with 62.6 % hypermethylated and 37.4 % hypomethylated. These DMRs were enriched in genes associated with critical processes such as metal ion binding, cell cycle regulation, and nervous system development. Promoter-specific methylation changes were notably pronounced, impacting pathways linked to neurodegenerative diseases, including Alzheimer's disease. Proteomic analysis identified 740 differentially expressed proteins (DEPs), with 366 upregulated and 374 downregulated in Pb-treated cells. Functional annotation revealed significant enrichment of DEPs in mitochondria, where Pb exposure disrupted processes related to oxidative phosphorylation, ion transport, and transmembrane processes. These proteomic changes aligned with the observed epigenetic modifications, reinforcing the role of Pb in impairing neuronal function via its effects on cellular energy metabolism and metal ion dynamics. Notably, Pb exposure disrupted Cu redox transitions between Cu(I) and Cu(II) as well as glutathione (GSH) activity, underscoring its impact on cellular metal homeostasis regulation and oxidative imbalance. In summary, this study provides a comprehensive view of how Pb exposure alters epigenetic and proteomic landscapes, disrupting key biological processes and pathways essential for neuronal health.]]> Wed, 31 Dec 1969 19:00:00 EST Beyond Koch's postulates: The pathobiome paradigm in grapevine esca disease. Gramaje D, Eichmeier A
FEMS Microbiol Ecol (Mar 2026)

Esca is one of the most damaging fungal diseases of grapevine and continues to defy Koch's postulates. Although Phaeomoniella chlamydospora, Phaeoacremonium minimum and Fomitiporia mediterranea are consistently associated with wood necrosis in esca-symptomatic vines, they also occur in asymptomatic vines and even in apparently healthy wood tissues without visible necrosis, and single-species but also mixed-species inoculations rarely reproduce the characteristic foliar symptoms. We hypothesize that esca is best understood as a stress-mediated pathobiome disorder of the grapevine holobiont rather than a predictable outcome of specific fungal combinations, shifting focus from pathogen identity to holobiont functional state and environmental context. In this Review, we integrate evidence from community ecology, vascular biology and multi-omics studies to link microbial community structure and activity with host hydraulics, defence and environmental drivers. Metabarcoding and metatranscriptomics indicate that symptom expression correlates with functional reprogramming of trunk-inhabiting fungi more than their mere presence, while metabolomics and epigenomics reveal localized physiological disruption combined with systemic regulatory responses. Climatic and edaphic stresses, particularly drought, are strongly associated with holobiont destabilization and dysbiosis, altering symptom expression without necessarily modifying pathogen occurrence. We propose a temporal, multi-phase model integrating colonization history, microbiome restructuring and host stress physiology through long-term feedbacks. This framework emerges through convergent multi-omics evidence and generates testable predictions for early detection, microbiome-informed biocontrol and resilience-oriented vineyard management strategies.]]> Wed, 31 Dec 1969 19:00:00 EST Artificial intelligence and multi-omics convergence in breast cancer: Revolutionizing diagnosis, prognostication, and precision oncology. Jiang B, Wu Y, Chen X, Jian C, Wang W
Crit Rev Oncol Hematol (Apr 2026)

Breast cancer (BC) is a highly heterogeneous malignancy and remains a major cause of cancer-related mortality among women worldwide. Advances in multi-omics profiling spanning genomics, transcriptomics, epigenomics, proteomics, and metabolomics have enabled finer subtype stratification and more comprehensive characterisation of tumour biology, thereby accelerating the discovery of diagnostic and prognostic biomarkers and actionable therapeutic targets. Nonetheless, translating multi-layer molecular signals into clinically robust decision support remains challenging because of the high dimensionality and heterogeneity of omics data, cross-cohort and cross-platform variability, and the fragmentation inherent to single-modality analyses. This review summarises how multi-omics studies have refined BC subtype definitions and advanced biomarker and target identification, and then synthesises recent progress in artificial intelligence, particularly deep learning, for integrating multi-omics with imaging, pathology, and clinical variables to improve diagnosis, risk stratification, prognosis prediction, and treatment response assessment. We critically examine representative multimodal integration frameworks and emerging deep learning architectures that learn both shared and modality-specific representations, which in many settings enable more accurate patient-level prediction than unimodal baselines. We further delineate key barriers to clinical translation, including cross-centre heterogeneity and inconsistent endpoint definitions, structural missingness of modalities in real-world workflows, inadequate cross-platform normalisation, limited interpretability and auditability, and a lack of prospective validation. Finally, we propose realistic next steps, including standardised and auditable preprocessing pipelines, missingness-aware fusion strategies, explainable and uncertainty-aware modelling, privacy-preserving multi-centre learning, and prospective, workflow-based evaluation. Collectively, these perspectives provide a roadmap for advancing multimodal AI-multi-omics integration toward reliable clinical deployment in BC management.]]> Wed, 31 Dec 1969 19:00:00 EST Single-cell epigenomics uncovers heterochromatin instability and transcription factor dysfunction during mouse brain aging. Amaral ML, Mamde S, Miller M, Hou X, Arzavala J, Osteen J, Johnson ND, Smoot EW, Yang Q, Eisner E, Zeng Q, Báez-Becerra CT, Olness J, Kern JC, Rink J, Barcoma A, Cho S, Cao S, Emerson N, Lee J, Willier J, Loe T, Jiao H, Zu S, Zhu Q, Preissl S, Wang A, Ecker JR, Behrens MM, Ren B
Cell Rep (Mar 2026)

The mechanisms regulating transcriptional changes during brain aging remain poorly understood. Here, we use single-cell epigenomics to profile chromatin accessibility and gene expression across eight mouse brain regions at 2, 9, and 18 months of age. In addition to a marked decline in progenitor populations involved in neurogenesis and myelination, we observe widespread and concordant age-associated changes in transcription and chromatin accessibility across both neuronal and glial cell types. These alterations are accompanied by dysregulation of master transcription factors and a shift toward stress-response programs driven by activator protein 1 (AP-1), indicating progressive drift in cellular identity with aging. We further identify region- and cell-type-specific heterochromatin loss, characterized by increased accessibility at H3K9me3-marked domains, activation of transposable elements, and upregulation of long noncoding RNAs, particularly in glutamatergic neurons. Together, these findings reveal age-related disruption of heterochromatin maintenance and transcriptional regulation, highlighting vulnerable brain regions, cell types, and molecular pathways in brain aging.]]> Wed, 31 Dec 1969 19:00:00 EST