geneimprint : Hot off the Press

'; ?> 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 Wed, 03 Dec 2025 22:44:40 EST Wed, 03 Dec 2025 22:44:40 EST jirtle@radonc.duke.edu james001@jirtle.com Integrating multi-omics data: Methods and applications in human complex diseases. Sibilio P, De Smaele E, Paci P, Conte F
Biotechnol Rep (Amst) (Dec 2025)

Over the past few decades, technological advancements and declining costs of high-throughput data generation have revolutionized biomedical research, enabling the collection of large-scale datasets across multiple omics layers-including genomics, transcriptomics, proteomics, metabolomics, and epigenomics. The analysis and integration of these datasets provides global insights into biological processes and holds great promise in elucidating the myriad molecular interactions associated with human diseases, particularly multifactorial ones such as cancer, cardiovascular, and neurodegenerative disorders. However, integrating multi-omics data presents significant challenges due to high dimensionality and heterogeneity. This review explores computational methods for integrating multi-omics data, with a particular focus on network-based approaches that offer a holistic view of relationships among biological components in health and disease. Furthermore, this review showcases a selection of recent, successful applications of multi-omics data integration, moving beyond theoretical methods to demonstrate their transformative potential in biomarker discovery, patient stratification, and guiding therapeutic interventions in specific human diseases.]]> Wed, 31 Dec 1969 19:00:00 EST CRISPR-Cas9-induced double-strand breaks disrupt maintenance of epigenetic information. Wang M, Zhang Y, Bi C, Li M
Genome Biol (Dec 2025)

CRISPR-Cas9 genome editing enables precise genetic modifications by introducing targeted DNA double-strand breaks (DSBs). While Cas9-induced DSBs are known to cause unintended on-target mutations, their impact on the epigenetic landscape remains unexplored.]]> Wed, 31 Dec 1969 19:00:00 EST A hitchhiker's guide to single-cell epigenomics: Methods and applications for cancer research. Moreno-Gonzalez M, Sierra I, Kind J
Int J Cancer (Jan 2026)

Genetic mutations are well known to influence tumorigenesis, tumor progression, treatment response and relapse, but the role of epigenetic variation in cancer progression is still largely unexplored. The lack of epigenetic understanding in cancer evolution is in part due to the limited availability of methods to examine such a heterogeneous disease. However, in the last decade the development of several single-cell methods to profile diverse chromatin features (chromatin accessibility, histone modifications, DNA methylation, etc.) has propelled the study of cancer epigenomics. In this review, we detail the current landscape of single-omic and multi-omic single-cell methods with a particular focus on the examination of histone modifications. Furthermore, we provide recommendations on both the application of these methods to cancer research and how to perform initial computational analyses. Together, this review serves as a referential framework for incorporating single-cell methods as an important tool for tumor biology.]]> Wed, 31 Dec 1969 19:00:00 EST Distinct transcriptomic and epigenomic responses of mature oligodendrocytes during disease progression in a mouse model of multiple sclerosis. Zheng C, HervÃ© B, Meijer M, Rubio RodrÃguez-Kirby LA, Guerreiro Cacais AO, Kukanja P, Kabbe M, Jimenez-Beristain T, Olsson T, Agirre E, Castelo-Branco G
Nat Neurosci (Dec 2025)

Multiple sclerosis (MS) is a chronic autoimmune disease that targets mature oligodendrocytes (MOLs) and their myelin. MOLs are heterogeneous and can transition to immune-like states in MS. However, the dynamics of this process remain unclear. Here, we used single-cell multiome assay for transposase-accessible chromatin and RNA sequencing targeting oligodendroglia (OLG) from the experimental autoimmune encephalomyelitis (EAE) MS mouse model at multiple disease stages. We found that immune OLG states appear at early disease stages and persist to late stages, which can be consistent with epigenetic memory of previous neuroinflammation. Transcription factor activity suggested immunosuppression in OLG at early disease stages. Different MOLs exhibit differential responsiveness to EAE, with MOL2 exhibiting a stronger transcriptional immune response than MOL5/MOL6, and showed divergent responses at the epigenetic level during disease evolution. Our single-cell multiomic resource highlights dynamic and subtype-specific responses of OLG to EAE, which might be amenable to modulation in MS.]]> Wed, 31 Dec 1969 19:00:00 EST From genes to lifestyle: A multi-dimensional framework for Alzheimer's disease prevention and therapy. Su L, Wang Y
Ageing Res Rev (Jan 2026)

Alzheimer's disease (AD) is a complex neurodegenerative disorder driven by multilayered molecular and cellular mechanisms that cannot be fully elucidated through single-omics approaches. Consequently, large-scale multi-omics integration-encompassing transcriptomics, epigenomics (e.g., methylation), and genetic association studies (GWAS/eQTL/mQTL)-has uncovered critical genetic and epigenetic networks underlying disease risk and progression.Based on these integrative insights, this review emphasized several genes-including KLHL21, SCN2B, ZNF415, and PITRM1-as potential contributors to AD pathogenesis. Notably, single-cell and spatial transcriptomics analyses revealed specific enrichment of these genes in astrocytes, underscoring the pivotal role of this cell type in AÎ² clearance, tau propagation, and neuroinflammation. Exercise interventions were shown to selectively modulate the expression of these genes, providing molecular support for the preventive and therapeutic potential of non-pharmacological lifestyle strategies. Drug repurposing analyses using DrugBank have identified promising therapeutic candidates, including FDA-approved agents (e.g., valproic acid, raloxifene, and clomipramine) and naturally derived compounds (e.g., quercetin and fisetin), which may modulate key AD-related pathways. Furthermore, emerging evidence of miRNA-gene regulatory networks suggested an additional layer of post-transcriptional control that may regulate responses to pathological stimuli. Collectively, these integrative insights advocated for a multidimensional precision medicine framework that spans genetic, cellular,network, and lifestyle levels of regulation. This shift from single-target therapeutics to an integrated "gene-cell-network-lifestyle" paradigm open new theoretical and translational avenues for delaying or mitigating AD progression.]]> Wed, 31 Dec 1969 19:00:00 EST A comparative review of single-cell atlases: mapping cellular diversity across species and tissues. Look K, Goh PE, Ming LC, Law SH, Tan SL, Tan EW, Ser HL, Goh BH
Cell Mol Life Sci (Dec 2025)

Single-cell sequencing (sc-seq) technologies have revolutionized biomedical research by enabling high-resolution analysis of cellular heterogeneity across multiple dimensions, including transcriptomics, epigenomics, and spatial profiling. These advances have led to the development of comprehensive single-cell atlases-reference maps of cell types and states across tissues and organisms, such as the Human Cell Atlas and Mouse Cell Atlas. These resources are foundational frameworks for investigating gene regulation, tissue architecture, and disease mechanisms. However, variations in biological focus, species representation, and dataset scale among available atlases necessitate a systematic comparative evaluation. This review provides an in-depth analysis of current single-cell atlases, assessing their scope, strengths, and limitations based on an updated framework derived from Hrovatin et al. We discuss the transformative role of sc-seq in oncology, immunology, and infectious disease research and highlight critical gaps in atlas development, including underrepresented species and tissue types. Finally, we propose key recommendations to guide future efforts in expanding, integrating, and standardizing single-cell atlas initiatives for enhanced translational impact.]]> Wed, 31 Dec 1969 19:00:00 EST [Expression of Concern] Gene therapy for human colorectal cancer cell lines with recombinant adenovirus 5 based on loss of the insulinâlike growth factor 2 imprinting. Sun H, Pan Y, He B, Deng Q, Li R, Xu Y, Chen J, Gao T, Ying H, Wang F, Liu X, Wang S
Int J Oncol (Jan 2026)

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, for the immunohistochemical data shown in Fig. 2B and C, the PBS/TUNEL panel in Fig. 2B appeared to be strikingly similar to the PBS/E1A panel shown in Fig. 2C. Furthermore, for the E1A experiments portrayed in Fig. 2C, portions of the data panels shown for the H101 and E1A groups also appeared to be strikingly similar, albeit with rotation of one of the panels. The authors were contacted by the Editorial Office to offer an explanation for this possible anomaly in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Oncology 46: 1759â1767, 2015; DOI: 10.3892/ijo.2015.2852].]]> Wed, 31 Dec 1969 19:00:00 EST Loss of function of chromatin remodeler OsCLSY4 leads to RdDM-mediated mis-expression of endosperm-specific genes affecting grain qualities. Pal AK, Rana S, Dey R, Shivaprasad PV
PLoS Genet (Dec 2025)

In plants, RNA-directed DNA methylation (RdDM) sequence-specifically targets transposable elements (TEs) and repeats, often in a tissue-specific manner. In triploid endosperm tissue, RdDM also acts as a parental dosage regulator, mediating spatio-temporal expression of genes required for its development. It is unclear how RdDM is initiated and established in endosperm. Rice endosperm-specific imprinted chromatin remodeler OsCLSY3 recruits RNA polymerase IV to specific genomic sites for silencing and optimal gene expression. Here we show that, in addition to OsCLSY3, ubiquitously expressed OsCLSY4 is also crucial for proper reproductive growth and endosperm development. Loss of function of OsCLSY4 led to reproductive and nutrient-filling defects in endosperm. Using genetic and molecular analysis, we show that both OsCLSY3 and OsCLSY4 play overlapping and unique silencing roles in rice endosperm, by targeting specific and shared genomic regions such as TEs, repeats and genic regions. These results indicate the importance of optimal expression of two OsCLSYs in regulating endosperm-specific gene expression, genomic imprinting and suppression of specific TEs. Results presented here provide new insights into the functions of rice CLSYs as upstream RdDM regulators in rice endosperm development, and we propose that functions of their homologs might be conserved across monocots.]]> Wed, 31 Dec 1969 19:00:00 EST Multiomics Insights into Epigenetic Mechanisms and Their Role as Biomarkers for Acute Coronary Syndrome. D'Agostino A, Rosalinda M, Salvatore M, Monica F
Heart Fail Clin (Jan 2026)

Acute coronary syndrome (ACS) is a complex cardiovascular condition driven by chronic inflammation, immune system imbalances, and epigenetic alterations. Recent research highlights the crucial role of epigenetic modifications in disease progression. Furthermore, differentially methylated regions influence expression in genes associated with immune signaling and cellular functions in ACS patients. ACS is a multifactorial disease driven by complex interactions between genetic, epigenetic, and environmental factors. By leveraging multiomics approaches, clinicians and researchers can uncover novel pathophysiological mechanisms and refine therapeutic strategies for improved cardiovascular outcomes in ACS patients. Integrating multiomics technologies with machine learning-driven analysis is revolutionizing our understanding of ACS.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenomics-guided precision oncology: Chromatin variants in prostate tumor evolution. Furlano K, Keshavarzian T, Biernath N, Fendler A, de Santis M, Weischenfeldt J, Lupien M
Int J Cancer (Jan 2026)

Prostate cancer is a common malignancy that in 5%-30% leads to treatment-resistant and highly aggressive disease. Metastasis-potential and treatment-resistance is thought to rely on increased plasticity of the cancer cells-a mechanism whereby cancer cells alter their identity to adapt to changing environments or therapeutic pressures to create cellular heterogeneity. To understand the molecular basis of this plasticity, genomic studies have uncovered genetic variants to capture clonal heterogeneity of primary tumors and metastases. As cellular plasticity is largely driven by non-genetic events, complementary studies in cancer epigenomics are now being conducted to identify chromatin variants. These variants, defined as genomic loci in cancer cells that show changes in chromatin state due to the loss or gain of epigenomic marks, inclusive of histone post-translational modifications, DNA methylation and histone variants, are considered the fundamental units of epigenomic heterogeneity. In prostate cancer chromatin variants hold the promise of guiding the new era of precision oncology. In this review, we explore the role of epigenomic heterogeneity in prostate cancer, focusing on how chromatin variants contribute to tumor evolution and therapy resistance. We therefore discuss their impact on cellular plasticity and stochastic events, highlighting the value of single-cell sequencing and liquid biopsy epigenomic assays to uncover new therapeutic targets and biomarkers. Ultimately, this review aims to support a new era of precision oncology, utilizing insights from epigenomics to improve prostate cancer patient outcomes.]]> Wed, 31 Dec 1969 19:00:00 EST From renal development to pathology: An analysis of the multilevel role of insulinâlike growth factor 2 (Review). Sun Y, Hao W, Liu W, Hu W
Mol Med Rep (Jan 2026)

Insulinâlike growth factor 2 (IGF2) is a multifunctional polypeptide hormone that serves important roles in embryonic development, metabolic regulation and disease pathogenesis. IGF2 expression is tightly regulated by genomic imprinting, which restricts transcription to the paternal allele. IGF2 modulates cellular processes, including proliferation, differentiation and metabolic homeostasis, by activating downstream signaling cascades via binding to IGF1 receptor, insulin receptor isoform A and IGF2 receptor. IGF2 is important for kidney development, promoting both nephron formation, and the functional maintenance of renal tubules and glomeruli. Aberrant IGF2 expression is associated with the pathogenesis of diverse renal diseases, including acute kidney injury, chronic kidney disease, diabetic nephropathy, renal cell carcinoma and Wilms' tumor. Under pathological conditions, IGF2 promotes renal fibrosis and promotes tumor expansion and progression by activating key signaling pathways such as the PI3K/Akt and TGFâÎ² pathways. Due to these roles, IGF2 has attracted growing clinical interest as a potential therapeutic target. The present review presents a comprehensive analysis of the structure and function of IGF2, its roles in renal pathophysiology, and its therapeutic potential, while outlining future research directions.]]> Wed, 31 Dec 1969 19:00:00 EST Analysis of Human Uniparental Embryonic Stem Cells Reveals New Putative Imprinted Loci. Kinreich S, Benvenisty N
Cell Prolif (Dec 2025)

Genomic imprinting, an epigenetic process resulting in parent-specific gene expression, is essential for normal development and growth. Disruption of imprinting leads to various developmental disorders and cancers, yet our understanding of the full repertoire of imprinted genes in humans remains incomplete. Here, we utilised androgenetic, parthenogenetic and biparental human embryonic stem cells and their neural derivatives to identify novel imprinted genes by analysing their methylome and transcriptome profiles. Our analysis revealed 12 novel putative imprinted genes distributed across four distinct loci, with six of them clustered in an uncharacterised imprinted region on chromosome 19. We identified potential imprinting control regions regulating this novel cluster, suggesting a coordinated regulatory mechanism. Notably, these imprinted genes are enriched in cancer-related pathways, with several showing isoform-specific imprinting patterns. Our analysis also revealed consistent DNA methylation aberrations in pluripotent stem cells at specific imprinted loci, highlighting potential epigenetic instability during culturing. These findings contribute to our understanding of genomic imprinting regulation in human development and highlight potential genomic regions for further investigation of imprinting-related disorders.]]> Wed, 31 Dec 1969 19:00:00 EST Decoding preterm birth: Non-Invasive biomarkers and personalized multi-omics strategies. Farzizadeh N, Najmi Z, Rosenbaum AJ, Amoozgar M, Hariri A, Aminbeidokhti M, Khosravi A, Zarrabi A
Dev Biol (Jan 2026)

A birth that occurs prior to 37 weeks of gestation is referred to as preterm birth (PTB). PTB is a health concern globally with significant outcomes including neonatal morbidity and mortality. Advancements in multi-omics have revolutionized the understanding of PTB pathogenesis, offering new opportunities for early prediction and risk categorization. This review highlights emerging liquid biomarkers derived from proteomic, metabolomic, genomic, transcriptomic, and epigenomic studies, emphasizing the integrative power of multi-omics approaches. Proteomic analyses have revealed key proteins in maternal and fetal compartments associated with inflammatory and extracellular matrix pathways, while metabolomics have identified lipid and metabolite profiles linked to energy metabolism and fetal development. Genomic and epigenomic studies have uncovered genetic variations and microRNAs involved in uterine contractility and immune modulation, providing novel insights into PTB's molecular underpinnings. Transcriptomic research further underscores the act of long non-coding RNAs (ncRNAs) in regulating gene expression and inflammatory responses. Multi-omics integration, coupled with machine learning models, has demonstrated superior predictive accuracy by synthesizing data across these domains, revealing intricate molecular interactions underlying PTB. Future research should prioritize longitudinal multi-omics studies to capture dynamic biological changes during pregnancy, expanding diverse population cohorts to enhance generalizability. Translating multi-omics insights into clinical practice necessitates collaborative efforts to develop cost-effective, accessible biomarker panels and establish standardized guidelines for implementation. These advancements hold the potential to transform prenatal care through personalized risk assessment and targeted preventive strategies, reducing the global burden of PTB.]]> Wed, 31 Dec 1969 19:00:00 EST Functional Mapping of Epigenomic Regulators Uncovers Coordinated Tumor Suppression by the HBO1 and MLL1 Complexes. Tang YJ, Xu H, Hughes NW, Ruiz P, Kim SH, Shuldiner EG, Lopez SS, Hebert JD, Karmakar S, Andrejka L, Dolcen DN, Boross G, Chu P, Kunder CA, Detrick C, Pierce SE, Ashkin EL, Greenleaf WJ, Voss AK, Thomas T, van de Rijn M, Petrov DA, Winslow MM
Cancer Discov (Dec 2025)

Epigenomic dysregulation is widespread in cancer. However, the specific epigenomic regulators and the processes they control to drive cancer phenotypes are poorly understood. We used a novel high-throughput in vivo method to perform iterative functional screens of >250 epigenomic regulators within autochthonous oncogenic Kras-driven lung tumors. We identified many previously unappreciated epigenomic tumor suppressor and tumor dependency genes. We show that a specific HBO1 complex and MLL1 complex are robust tumor suppressors in lung adenocarcinoma. Histone modifications generated by the HBO1 complex are frequently reduced in human lung adenocarcinomas and are associated with worse clinical features. HBO1 and MLL1 complexes co-occupy shared genomic regions, affect chromatin accessibility, and control the expression of canonical tumor suppressor genes and lineage fidelity. The HBO1 complex is epistatic with the MLL1 complex and other tumor suppressor genes in lung adenocarcinoma development. Collectively, these results provide a phenotypic roadmap of epigenomic regulators in lung tumorigenesis in vivo.]]> 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 Expansion omics: from expansion microscopy to spatial omics. Dong Z, Xiang W, Jiang W, Guo T
Mol Syst Biol (Dec 2025)

Tissue expansion, originally developed for super-resolution imaging, has become a foundation for expansion omics (ExO), a growing field that uses physical tissue expansion to enable spatially resolved omics profiling. In this perspective, we explore how ExO integrates multi-omics through chemical anchoring strategies that ensure selective retention of diverse molecular species, together with improved spatial resolution from the subcellular resolution for profiling to the sub-nanometer scale for imaging, allowing precise detection of biomolecules and their link with biological function. These capabilities have empowered tissue expansion to be successfully applied across multiple spatial omics modalities, including epigenomics, transcriptomics, proteomics, and lipidomics, enabling high-resolution mapping of chromatin states, gene expression, protein localization, and lipid distributions. Moreover, ExO supports spatial multi-omics approaches that jointly capture and correlate multiple biomolecular dimensions within the same tissue context. However, challenges remain in expansion resolution, molecular retention, hydrogel adaptability, data scalability, and AI-driven analysis. As tissue expansion evolves, its integration of super-resolution imaging and spatial omics establishes it as a core technology for whole-slide, single-cell multi-omics and the development of the Artificial Intelligence Virtual Cell, advancing spatial biology and medicine.]]> 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 Crosstalk between skeletal muscle and the brain during physical activity - in search of epigenetic mechanisms. Boycott C, Kilanczyk E, Zhang HA, Zhang J, Abolhassani A, Kubiak M, Celichowski J, KryÅciak K, Gruszka D, Sliwowska JH, Stefanska B
Epigenetics (Dec 2025)

Recent research highlights the crucial role of muscle-brain crosstalk in metabolic regulation, particularly in individuals with type 2 diabetes and obesity. Myokines, protein hormones secreted by skeletal muscle, play a crucial role in this communication, influencing brain functions such as neuroplasticity, memory, and mood. Specific myokines like cathepsin B, FNDC5/irisin and interleukin-6Â have been identified as key players in this muscle-brain axis. Physical activity modulates the production of these molecular factors, enhancing muscle-brain crosstalk and influencing cellular interactions. Moreover, exercise training may lead to adaptive long-term changes in gene expression, mediated by epigenetic regulators. Metabolic pathways activated during exercise can directly impact epigenetic marks by modulating the availability of metabolic intermediates required for these modifications. In the present review, we summarize the latest findings on the association between obesity/diabetes and cognitive impairment due to hippocampal dysfunction, and elaborate on how exercise influences cognitive functions via the communication between skeletal muscle and the brain. We focus on the underlying mechanisms responsible for the muscle-brain crosstalk, emphasizing dynamic changes in the epigenome and epitranscriptome, which sheds light on novel preventive and therapeutic approaches to combat obesity and cognitive decline.]]> Wed, 31 Dec 1969 19:00:00 EST Single-cell multi-omics characterize colorectal tumors, adjacent healthy tissue and matched (tumor) organoids identifying CRC-unique features. Yu Z, Derksen M, Te Pas BM, LadstÃ¤tter S, Overmeer R, Brazda P, van de Wetering M, Pourfarzad F, Vries RGJ, Megchelenbrink W, Bock C, Altucci L, Stunnenberg HG
Int J Cancer (Dec 2025)

Colorectal cancer (CRC) arises in the colorectal tissue driven by genetic disorder or the accumulation of somatic mutations, leading to abnormal epithelial cell growth. In this study, we employed single-nucleus multi-omics analysis, including single-nucleus RNA-seq and single-nucleus ATAC-seq, on over 100,000 high-quality nuclei to investigate the molecular landscape of both primary tissue and patient-derived organoids (PDOs). Our analysis showed that normal PDOs (N-PDOs) derived from tissue adjacent to tumors replicate the cellular composition and differentiation trajectory of colorectal crypts. In contrast, tumor PDOs (T-PDOs) showed patient-specific transcriptomic and epigenomic heterogeneity yet consistently maintained a stem cell-like state. T-PDOs retained the somatic mutation profile of the primary tumor while also exhibiting de novo mutations not detected in either the primary tumor or N-PDOs. Notably, inferred cell-cell interaction analysis highlighted the activin signaling pathway as a potential unique feature of fibroblast-epithelial interactions within the tumor microenvironment. This study provides a comprehensive view of the transition from normal to malignant colorectal epithelium and underscores the utility of PDOs as a faithful model for capturing both conserved and patient-specific features of colorectal cancer.]]> Wed, 31 Dec 1969 19:00:00 EST The omics revolution in obesity: from molecularsignatures to clinical solutions. Mustafa M, Arafat AA, Alhazzani W, Kunnathodi F, Azmi S, Anvarbatcha R, Ahmad I, Alotaibi HF
Mol Omics (Dec 2025)

Obesity is a multifactorial condition projected to affect over half of the global population by 2035, posing significant clinical and socioeconomic challenges. Traditional metrics such as body mass index lack precision in predicting individual risk, disease progression, and therapeutic response due to the heterogeneous nature of obesity. Advances in omics technologies such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics have enabled the identification of molecular subtypes and candidate biomarkers that offer deeper insights into obesity pathophysiology. Genomic studies have revealed hundreds of loci associated with obesity related traits, while polygenic risk scores offer modest improvements in early risk prediction. Epigenomic profiling, particularly deoxy ribose nucleic acid (DNA) methylation signatures such as those at carnitine palmitoyl transferase 1A () and hypoxia inducible factor 3 subunit alpha (), has uncovered modifiable pathways linked to adiposity and metabolic dysfunction. These findings are increasingly being integrated with other omics layers to improve stratification and therapeutic targeting. Metabolomic subtypes, including ceramide driven insulin resistance and branched chain amino acid (BCAA) dominant dysregulation, have shown potential in guiding treatment selection, such as sodium glucose cotransporter 2 (SGLT2) inhibitors or glucagon like peptide-1 (GLP-1) agonists. Proteomic markers like proprotein convertase subtilisin/kexin type 9 () and retinol binding protein 4 () are being evaluated for cardiovascular risk stratification independent of body mass index (BMI). Integrative multiomics frameworks and AI driven models are beginning to bridge molecular data with clinical phenotypes, enabling patient stratification and risk modeling. However, most findings remain in research grade environments, and clinical translation is limited by cohort diversity, data harmonization challenges, and the lack of standardized validation protocols. This review synthesizes evidence from single and multiomics studies, highlights emerging biomarkers and molecular subtypes, and discusses the potential of omics guided frameworks to inform precision obesity care.]]> Wed, 31 Dec 1969 19:00:00 EST