SEARCH · Search PubMed

Results for “DNA methylation profiling”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

PubMed2026

Cross-Platform Concordance in DNA Methylation Based Classification of CNS Tumors.

DNA methylation profiling enables precise classification of pediatric central nervous system (CNS) tumors. Oxford Nanopore Technologies (ONT) offers same-day, single-sample methylation readouts, but its concordance with Illumina EPIC arrays in routine diagnostic tasks remains incompletely defined. We profiled 23 pediatric tumors (18 CNS, 5 non-CNS) by EPIC arrays and ONT. Methylation profiles from both platforms were classified with crossNN (brain model or pan-cancer model); ONT data were additionally classified with Rapid-CNS2 and Sturgeon. We compared (i) classifier agreement with integrated histology (w/o NGS) at family/class levels, (ii) pass-rate above platform-specific score cutoffs, (iii) cross-platform concordance of copy-number variation (CNV), and MGMT promoter methylation status. In CNS cases, ONT and EPIC methylation profiles demonstrated strong correlation, except for a single outlier (P2), which was excluded from further analysis. Comparative assessment of the two platforms showed that: (a) Molecular classification of CNS tumors using the crossNN classifier was consistent with histology (w/o NGS) at the family level in all cases. (b) Copy-number profiles showed high concordance between platforms. (c) MGMT promoter methylation status matched in 94% of cases (16/17). When comparing ONT-specific analysis pipelines using the ONT data, the Rapid-CNS2 pipeline yielded the most reliable class level assignments with 94% (16/17) concordance with the histopathological diagnosis, which marginally exceeded the crossNN and sturgeon classifiers. In non-CNS tumors, the pan-cancer model produced low-confidence outputs with poor agreement with histology (w/o NGS) (only 1/5 concordant), indicating limited readiness for these entities. In conclusion, ONT enables same-day, clinically reliable family-level CNS tumor classification with high concordance to arrays, while EPIC retains a modest class-level edge. A key limitation of ONT is its reliance on fresh-frozen DNA and on classifiers originally built around array-derived CpG sites, rather than on models developed natively from ONT data.

DNA methylation↗

PubMed2026

Multi-omics analysis reveals coordinated epigenetic dysregulation in atrazine-induced dopaminergic neurotoxicity.

Atrazine (ATR), a widely used triazine herbicide, has been linked to neurotoxicity, yet the epigenetic mechanisms underlying its dopaminergic effects remain unclear. This study investigated whether coordinated miRNA dysregulation and DNA methylation alterations contribute to ATR-induced Parkinson's disease (PD)-like neurotoxicity. Male Sprague-Dawley rats were administered ATR (50 mg/kg/day) for 90 days, resulting in motor and cognitive deficits with dopaminergic dysfunction, including increased α-synuclein and reduced tyrosine hydroxylase expression. Small RNA sequencing identified 72 differentially expressed miRNAs in the substantia nigra, enriched in PI3K-Akt, MAPK, and Ras signaling pathways. In a cohort of six PD patients and six matched controls, genome-wide DNA methylation profiling revealed 4694 differentially methylated positions, predominantly hypomethylated, with overlapping enrichment in neuronal signaling pathways. Weighted gene co-expression network analysis identified a PD-associated module strongly correlated with disease status (r = -0.95, P < 0.001). Multi-omics integration identified CASP3 as a central hub gene. External validation supported CASP3 relevance in PD (AUC = 0.833), and molecular docking suggested potential ATR-CASP3 interaction. Further analysis predicted upregulated miR-3552 as a potential upstream regulator of CASP3. These findings indicate that ATR-induced neurotoxicity may be mediated through the miR-3552/CASP3 signaling axis, ultimately regulating apoptosis and contributing to neurodegeneration.

Animals↗

PubMed2026

Primary Tumor Epigenetic and Transcriptomic Alterations Associated with Nodal Burden and Metastatic Risk in ER+/HER2- Breast Cancer.

De-escalation of axillary surgery has resulted in the loss of pathologic nodal information, yet the extent of lymph node involvement remains an important determinant of treatment decisions in estrogen receptor-positive (ER+)/HER2- disease. We examined whether primary tumors differed molecularly according to the extent of this regional dissemination. Genome-wide DNA methylation profiling of primary ER+/HER2- tumors from 47 patients with pN1 (n = 29) vs. >pN1 (n = 18) disease showed differences concentrated at promoters of developmental and cell-adhesion genes. By integrating methylomes with transcriptomes from the TCGA-BRCA cohort (n = 148) and clinical outcomes from KM Plotter (RFS, n = 1154; OS, n = 442; DMFS, n = 423), we identified four genes (ARL10, RIC3, CXCL14, KCNH2) showing concordant molecular and clinical associations, from which we derived the Lymph-node Involvement Outcome Numerator (LION) score. Lower LION scores were observed in metastatic lesions from the AURORA US cohort (n = 45). In SCAN-B (n = 3969), lower scores were associated with shorter distant recurrence-free intervals (HR = 0.38; 95% CI 0.23-0.62); this association persisted after adjustment for age, nodal and tumor category but was lost after adjustment for histological grade (HR = 0.83; 95% CI 0.48-1.44), indicating that the score and grade capture overlapping biology. These findings suggest that primary tumors already display coordinated epigenetic and transcriptional alterations associated with the extent of metastatic dissemination.

Humans↗

PubMed2026

Long-term (>7-year) parental consumption of genetically modified maize (Cry1Ab/Cry2Aj and EPSPS) induces no adverse sperm DNA methylation alterations across two generations of cynomolgus monkeys.

This study assessed the long-term safety of genetically modified (GM) maize from a male reproductive perspective, using a non-human primate model. We analyzed the sperm DNA methylation profiles in cynomolgus monkeys fed GM maize, non-GM parental maize, or a conventional diet over two generations (F0/F1). Whole-genome bisulfite sequencing (WGBS) revealed no significant differences in global methylation levels among groups. The identified differentially methylated regions (DMRs) were short, enriched in non-regulatory genomic areas, and did not cluster after treatment. Functional enrichment analysis showed that DMR-associated genes were consistently involved in the same core biological pathways (e.g., mTOR and Wnt signaling) across all dietary comparisons. These findings indicate that GM maize consumption did not induce specific adverse epigenetic alterations in sperm, with the observed changes reflecting common physiological adaptations to dietary variations rather than GM-related effects.

Animals↗

PubMed2026

Epigenetic and immunological alterations in umbilical cord blood of overweight/obese women with gestational diabetes mellitus: insights into DNA methylation signatures and immune cell dysregulation.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication associated with adverse maternal and neonatal outcomes. Epigenetic modifications may reflect intrauterine metabolic exposure and contribute to immune and metabolic alterations. This study aimed to explore DNA methylation profiles in umbilical cord blood from overweight and obese women with and without GDM. METHODS: Umbilical cord blood samples from 30 overweight/obese pregnant women (with and without GDM) were analyzed using the Illumina 850 K methylation array to identify differentially methylated positions (DMPs) and regions (DMRs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to assess the functional relevance of methylation changes. Immune cell composition was estimated using deconvolution analysis and further examined in an independent single-cell RNA sequencing (scRNA-seq) cohort. Lasso regression was applied to identify CpG sites associated with GDM status and construct a preliminary methylation-based classification model. RESULTS: A total of 23,331 hypermethylated and 29,501 hypomethylated DMPs were identified between women with and without GDM, with hypomethylation predominating. Enrichment analyses indicated associations with neurodevelopmental pathways, metabolic processes, immune regulation, and epigenetic modification. Immune deconvolution analysis suggested reduced proportions of CD4+ T cells (p < 0.05) and a trend toward decreased NK cells in the GDM group, alongside increased CD8+ T cells and neutrophils. Seven CpG sites were selected for model construction and demonstrated strong discriminatory performance within this cohort. CONCLUSION: This exploratory study identifies distinct cord blood DNA methylation patterns associated with GDM in overweight/obese pregnancies. The findings suggest potential links between epigenetic alterations and immune cell composition in GDM-exposed offspring. The identified CpG signature warrants further validation in larger, prospective cohorts to determine its clinical applicability.

Humans↗

PubMed2026

Epigenome-wide analysis of DNA-methylation signatures following climate-related disasters.

BACKGROUND: Floods and tropical cyclones (TCs), two of the most frequent and costliest climate-related disasters worldwide, have been linked to sustained health risks extending beyond acute hazards. However, evidence on the underlying epigenetic mechanisms remains scarce. We aimed to characterize DNA methylation patterns associated with exposure to floods and TCs of varying intensities. METHODS: We collected peripheral blood samples from 479 women (132 twin pairs and 215 of their sisters) across Australia. Blood-derived DNA methylation profiles were assessed using the Illumina HumanMethylation450 BeadChip array. Daily flood and TC exposure data for the 6 years preceding each blood draw were obtained from the Dartmouth Flood Observatory and the International Best Track Archive for Climate Stewardship, respectively, and linked to participants based on residential addresses. Using a within-sibship analytical framework that accounted for shared familial factors and other relevant covariates, we examined associations between flood and TC exposures of varying intensities and site-specific methylation at each cytosine-guanine dinucleotide (CpG). Differentially methylated regions (DMRs) were identified using a combination of the comb-p and DMRcate algorithms. RESULTS: There were 164 CpGs and 219 DMRs associated with flood and TC exposures (Bonferroni-adjusted p value < 0.05), mapping to 242 genes enriched in pathways related to inflammation and immune regulation. These genes have been implicated in a wide range of human diseases or phenotypes. The number of differentially methylated CpGs increased with more recent and higher-intensity exposures. Intensity-dependent gene regulation was observed, with genes such as AMT and C22orf45 consistently implicated across various exposure levels, whereas RNF39 and ACY3 emerged only at higher intensities. CONCLUSIONS: Exposures to floods and TCs were associated with differentially DNA methylated signals across the human genome, exhibiting intensity-dependent patterns. The identified signals and related gene pathways may shed light on the biological mechanism underlying the profound health effects of climate-related disasters.

Humans↗

PubMed2006

Epigenetic regulation of the tumor suppressor gene TCF21 on 6q23-q24 in lung and head and neck cancer.

The identification of tumor suppressor genes has classically depended on their localization within recurrent regions of loss of heterozygosity. According to Knudson's two-hit hypothesis, the remaining allele is lost, either genetically or, more recently identified, through epigenetic events. To date, retrospective analyses have determined promoter methylation as a common alternative alteration in cancer cells to silence cancer-related genes. Here we report an application of restriction landmark genomic scanning that allows for DNA methylation profiling along a region of recurrent loss of heterozygosity at chromosome 6q23-q24. This approach resulted in the identification of a tumor suppressor gene, TCF21, which is frequently lost in human malignancies. We demonstrate that TCF21 is expressed in normal lung airway epithelial cells and aberrantly methylated and silenced in the majority of head and neck squamous cell carcinomas and non-small-cell lung cancers analyzed. TCF21 is known to regulate mesenchymal cell transition into epithelial cells, a property that has been shown to be deficient in carcinomas. We further demonstrate that exogenous expression of TCF21 in cells that have silenced the endogenous TCF21 locus resulted in a reduction of tumor properties in vitro and in vivo.

Animals↗

PubMed2026

CpG hypermethylation and WNT/AP-1 cooperativity define the epigenetic landscape and a clinical subgroup of high-risk pediatric adrenocortical carcinoma.

Pediatric adrenocortical tumors are rare, clinically heterogeneous neoplasms with unpredictable outcomes and limited treatment options. Through integrated multi-omic analysis of 214 pediatric adrenocortical tumors combining DNA methylation profiling, transcriptomics, chromatin accessibility, and spatial deconvolution, we identify four distinct risk groups. A high-risk subgroup is characterized by CpG island hypermethylation, chromosomal instability, and dismal survival. These tumors exhibit transcriptional co-activation of WNT signalling and activator protein-1 transcriptional programs and display balanced admixture of zona glomerulosa and zona fasciculata/reticularis-like cells. Spatial analysis reveals zona glomerulosa cells as WNT signaling hubs driving intercellular crosstalk. Mechanistically, the histone deacetylase inhibitor entinostat reverses promoter methylation, silences activator protein-1 activity, and induces apoptotic reprogramming in tumor models. These findings establish a molecular framework for risk stratification and identify actionable therapeutic vulnerabilities, providing an essential resource for studying this molecularly uncharted pediatric malignancy.

Humans↗

PubMed2026

Epigenetic aging and autosomal methylation remodeling in Anderson-Fabry disease.

Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disorder characterized by marked clinical heterogeneity and incompletely understood genotype-phenotype correlations. While X-chromosome inactivation has been extensively investigated, the contribution of autosomal epigenetic mechanisms to phenotypic variability remains poorly defined. Here, we performed an exploratory genome-wide DNA methylation analysis in 32 AFD patients (22 females and 10 males; mean age 51.7 years) recruited within a multicenter regional research project in Calabria (Italy). DNA methylation profiling was conducted using the Infinium MethylationEPIC v2.0 array. The analysis integrated two complementary approaches: differential methylation analysis and evaluation of biological aging through multiple epigenetic clocks, including Horvath, Hannum, PhenoAge, Skin & Blood, GrimAge, and DunedinPACE. Exploratory methylome-wide analysis identified a limited set of CpG loci showing nominal evidence of methylation differences between carriers of pathogenic and non-pathogenic variants; however, none remained statistically significant after correction for multiple testing. Annotation of the top-ranking nominal CpG associations highlighted genes involved in biological processes including vascular regulation, intracellular trafficking, cytoskeletal organization, immune signaling, and lipid metabolism. No significant differences between groups were observed for the conventional epigenetic age-acceleration measures examined. In contrast, carriers of pathogenic variants showed significantly higher DunedinPACE values (p = 0.0328), indicating a faster estimated pace of biological aging. This finding suggests that DunedinPACE may capture aspects of the cumulative systemic burden associated with pathogenic GLA variants, although confirmation in larger independent cohorts is required. Overall, this pilot epigenomic study provides preliminary evidence that autosomal epigenetic remodeling and biological aging acceleration may contribute to phenotypic heterogeneity in AFD.

Anderson-Fabry disease↗

PubMed2026

Primary mismatch repair deficient glioma, IDH-wildtype and H3-wildtype: A giant cell tumor with potential for long-term survival occurring at all ages.

BACKGROUND: Replication repair deficiency is associated with increased risk of developing malignant gliomas. The aim of this study was to investigate primary mismatch repair deficient gliomas (PMMRDGs), a group of IDH-wildtype and H3-wildtype gliomas that is enriched among patients with CMMRD and Lynch syndrome. METHODS: We investigated how PMMRDGs differ from other gliomas with respect to DNA methylation profile, genomic alterations, histopathology, and clinical outcomes. RESULTS: PMMRDGs occur in pediatric, adolescents and the elderly, falling in two related methylation clusters and are characterized by a high frequency of replication repair deficiency. Histology showed multinucleated giant cells, and immunohistochemistry demonstrated loss of MMR protein expression. Survival analysis revealed long-term survival in patients with high mutational burden (>50 mut/Mb) and an intact chromosome 9p region, which was validated in an independent reference cohort. CONCLUSIONS: Overall, our findings indicate that PMMRDGs represent a distinct type of IDH-wildtype gliomas with potential for long-term survival likely driven by immune activation.

Humans↗

PubMed2026

Integrative methylation and miRNA dysregulation in dlPFC reveal distinct molecular signatures of suicide and non-suicide subtypes in major depressive disorder.

AIM: Major depressive disorder (MDD) is a leading cause of disability and carries a high risk of suicide. MicroRNAs (miRNAs) are epigenetic regulators implicated in MDD and can be regulated by DNA methylation, potentially reshaping downstream gene networks. We investigated methylation-linked miRNA dysregulation and explored whether these changes are specifically associated with suicide among MDD patients. METHODS: Genome-wide DNA methylation profiling of the dorsolateral prefrontal cortex from 15 MDD patients who died by suicide (MDD+S), 17 MDD patients who died from causes other than suicide (MDD-S), and 16 controls (C) using the Illumina 850K MethylationEPIC array was integrated with small RNA sequencing-based miRNA quantification to identify miRNA-associated differentially methylated probes (DMPs), link methylation to miRNA expression, and infer downstream targets and pathways. RESULTS: Differential methylation analysis (P ≤ 0.05) revealed 139 miRNA-linked DMPs in C vs. MDD+/-S, 135 in C vs. MDD-S, 179 in C vs. MDD+S, and the highest in MDD+S vs. MDD-S (235). CpG-miRNA pairing (within 1500kb promoter) followed by Spearman correlation identified inverse associations between CpG β values and miRNA expression, with the most consistent signals in suicide-status-stratified subsets, including cg06341821-hsa-miR-574-3p and cg25451306-hsa-miR-2110 in MDD+S-related contrasts, and cg06179179-hsa-miR-595 in MDD-S-related contrasts. High-confidence target prediction and ClueGO enrichment indicated distinct biology: miR-595 target genes in MDD-S were enriched for interferon/innate immune signaling, whereas miR-2110 target genes in MDD+S were enriched for ligand-gated ion channel activity and synaptic/receptor signaling. CONCLUSION: This integrated approach identifies methylation-regulated miRNA pathways that may play key roles in the molecular pathogenesis of MDD and suicide.

Humans↗

PubMed2025

Genome-wide methylation biomarkers and biological aging in patients with bipolar disorder characterized for lithium response.

BACKGROUND: Epigenetic mechanisms might play a role in modulating susceptibility to bipolar disorder (BD) and response to lithium, the mainstay treatment for BD. Additionally, individuals with BD experience accelerated biological aging. METHODS: We compared blood DNA methylation profiles measured with EPIC v.2.0 arrays between patients with BD (33 lithium responders and 31 nonresponders) and nonpsychiatric controls (n = 32), as well as based on long-term lithium response. In addition, we compared cellular aging between these groups using epigenetic age, pace of aging, and, for the first time, transcriptional age acceleration based on bulk RNA sequencing in 93 patients and 56 controls. RESULTS: We identified 191 differentially methylated positions (DMPs) and 8 differentially methylated regions between patients with BD and controls, located in genes enriched for "Postsynaptic Density" (odds ratio = 6.81, p = 0.001). No DMP was significantly associated with lithium response after multiple testing correction. Patients showed a significantly higher biological age acceleration than controls based on two epigenetic clocks (GrimAge, Mann-Whitney U = 551, p = 0.0009; GrimAge2: U = 477, p = 9.0E-05) and pace of aging (DunedinPACE, t = 3.01, p = 0.003), but not on transcriptional age. While we observed no significant difference in epigenetic aging based on lithium response, lithium responders showed lower epigenetic acceleration using all clocks, with a trend observed using the PhenoAge clock (t = 1.97, p = 0.053). CONCLUSIONS: Our findings point to methylation patterns characterizing BD and support the hypothesis of accelerated cellular aging in BD.

Humans↗

PubMed2026

Genetic-epigenetic interactions (meQTLs) in orofacial clefts etiology.

Understanding how genetic variants influence disease risk through molecular mechanisms remains a central challenge in complex disease genetics. Nonsyndromic orofacial clefts (OFCs) exemplify this challenge, with most risk loci residing in non-coding regions. We hypothesized that common genetic variants influence OFC risk by modulating DNA methylation at regulatory elements through methylation quantitative trait loci (meQTLs). We analyzed 10 OFC-associated SNPs against genome-wide DNA methylation profiles in 409 cases and 456 controls, identifying 23 potential meQTLs. Findings were validated using 358 cleft-discordant sibling pairs with MethyLight assays. We performed formal mediation analysis, genotype-tissue interaction and cross-referenced with the mQTL Database to assess developmental timing. Nine meQTLs were validated, including rs987525 (8q24)-cg16561172 (MYC) (P = 9.6 × 10⁻⁶), which mapped to a mesendoderm-active enhancer upstream of MYC. Genotype × tissue interaction confirmed tissue-specificity (P = 1.00 × 10- 3), with stronger effects in oral-derived tissue (saliva). Additional validated SNP-CpG associations involved MAFB-PLCG1, NOG-PPM1E, FOXE1-FRZB, and SPRY2-LGR4. While effect sizes correlated between tissues (r = 0.81), formal mediation analysis indicated individual CpG sites do not fully mediate SNP-phenotype relationships, suggesting coordinated epigenetic mechanisms. Most associations showed peak effects during childhood, while 8q24 showed unique adult-specific patterns. We identified genetic variants influencing methylation at craniofacial regulatory elements, and provided a mechanistic link for a major risk locus, 8q24, with tissue-specific effects in saliva. While individual CpG sites did not fully mediate the genetic risk, our findings identified specific regulatory regions where coordinated epigenetic changes may contribute to OFC susceptibility.

Humans↗

PubMed2026

A MAGIBU-based model for pediatric and juvenile CNS tumors: an in-house epigenetic decision-support framework compared with online DNA methylation classifiers.

Background: DNA methylation profiling is a tool that provides key support for central nervous system (CNS) tumor classification. However, diagnostically ambiguous pediatric cases may result in discordant outputs across classifiers. We developed MAGIBU, a cross-platform, projection-based framework that embeds individual methylomes into a fixed CNS reference landscape, ranking diagnostic entities by local epigenetic proximity to support clinician-led integrative diagnosis. Methods: As a proof-of-concept, we evaluated MAGIBU in eight morphologically challenging pediatric/juvenile CNS tumors with unresolved diagnoses after institutional and central pathology review. To establish a benchmark in the absence of a definitive histopathological ground truth, a consensus epigenetic reference was defined a priori for cases showing concordant results between the Heidelberg CNS Tumor Methylation Classifier and Methylscape Analysis. Comparisons were also performed with Epigenomic Digital Pathology (EpiDiP). To validate MAGIBU beyond this discovery cohort, performance was assessed at the family level across the CNS methylation spectrum (n = 678, 28 methylation families), on non-array platforms (whole-genome bisulfite sequencing and Oxford Nanopore), and in a focused analysis of the low-grade glioma and diffuse midline glioma compartment across four independent cohorts (n = 670). Results: In the discovery cohort, MAGIBU achieved high concordance with the consensus reference (Cohen's κ = 0.855), outperforming EpiDiP (κ = 0.278), which frequently placed low-grade tumors in proximity to higher-grade reference regions. Conclusions: MAGIBU provides a stable, quantitative differential diagnosis framework that mitigates the limitations of rigid categorical assignments. By leveraging a distance-based proximity metric, it offers a transparent decision-support tool that integrates effectively with clinical, radiological, and molecular data. While performance is inherently dependent on reference atlas composition, MAGIBU represents a robust complementary approach for the diagnostic workup of ambiguous CNS tumors.

Brain↗

PubMed2026

Comparative genomic analysis of Streptococcus parasuis and Streptococcus suis reveals mobile element-associated enrichment of antimicrobial resistance and lack of detectable same-MGE colocalization with virulence-associated genes within stable species boundaries.

Streptococcus suis is a major porcine pathogen and a zoonotic agent that causes meningitis and septicemia in humans. Streptococcus parasuis, a recently recognized close relative, remains poorly characterized with regard to its clinical significance and genomic features. In this study, we generated a single-contig closed genome assembly with genome-wide DNA methylation profiles for S. parasuis strain A1, isolated from a diseased pig in Xinjiang, China, and complemented in silico genomic predictions with isolate-level experimental validation of antimicrobial resistance (AMR) genotypes, virulence genotypes, and phenotypic susceptibility for this reference strain. Using this high-quality genome as a reference anchor, we performed comparative genomic analyses across 195 streptococcal genomes, comprising 15 S. parasuis and 180 S. suis strains, to distinguish genome-level co-occurrence of resistance and virulence determinants from their physical colocalization on the same mobile genetic element (MGE).Species boundaries remained clearly delineated at the genomic level, with a median interspecies average nucleotide identity (ANI) of approximately 86.0%, compared with intraspecies ANI medians of 97.5% for S. parasuis and 96.2% for S. suis. Pangenome analysis identified 12,693 gene clusters, of which 1086 were core clusters, and functional annotation revealed significant differences in accessory gene repertoires between the two species. Within this stable genomic framework, S. parasuis genomes carried a higher AMR gene burden; strain A1 harbored 10 AMR genes, multiple virulence-associated genes, three genomic islands, and eight prophage regions. For strain A1, PCR validation confirmed six AMR genes and six virulence genes, and disk diffusion testing demonstrated a multidrug-resistant phenotype consistent with the genotypic profile.Among 235 predicted mobile elements, 19 harbored AMR genes and seven carried Virulence Factor Database (VFDB) homologs, but none carried both categories simultaneously. This finding reflects a lack of detectable same-MGE colocalization under the applied annotation and assembly framework; it should not be interpreted as evidence of biological physical decoupling. Under a random-placement model, the expected number of co-carrying regions was only 0.57, and the probability of observing zero co-carrying regions was P = 0.55. This negative result should be interpreted with caution, given the limited number of cargo-bearing regions and the predominantly draft status of most genomes. Furthermore, the A1 genome contained multiple restriction-modification systems, showed depletion of several methylation motif families in mobile regions, and had limited CRISPR spacer matching evidence, suggesting prior exposure to the relevant sequence space. None of the genomes met our predefined criteria for whole-genome convergence.Collectively, our results support a model in which S. parasuis accumulates AMR-related genes in a modular fashion via mobile elements within stable species boundaries, with no detectable same-MGE colocalization of AMR and virulence determinants under our analytical pipeline. These findings imply that AMR surveillance strategies for this species should prioritize tracking mobile genetic elements rather than inferring wholesale genomic convergence toward S. suis.

Streptococcus suis↗

PubMed2026

"Updates on diagnostic and prognostic molecular biomarkers of CNS tumors".

The diagnosis and classification of central nervous system (CNS) tumors has undergone a paradigm shift over the past decade, evolving from a purely histology-based approach to an integrated framework that incorporates molecular and epigenetic features. This review summarizes recent updates in key genomic and epigenomic biomarkers across major CNS tumor categories, with a focus on their diagnostic, prognostic, and therapeutic implications. DNA methylation profiling has emerged as a valuable tool for tumor classification, subgrouping, and grading, complementing traditional histopathologic assessment. Across diffuse gliomas, newly characterized molecular alterations have refined grading criteria and clarified the boundaries between tumor types, including important caveats about the use of individual molecular features as sole diagnostic criteria. In ependymomas, medulloblastomas, atypical teratoid/rhabdoid tumors, meningiomas, pineal tumors, and embryonal tumors, methylation profiling now defines biologically and clinically meaningful subgroups that inform risk stratification and treatment selection. The emerging recognition of mismatch repair-deficient gliomas and fusion-driven tumor entities further underscores the expanding complexity of CNS tumor taxonomy. As molecular technologies continue to advance, the integration of genomic, epigenomic, histopathologic, and clinical data will be essential to improving diagnostic precision, guiding therapy, and ultimately enhancing patient outcomes.

Embryonal↗

PubMed2026

Beyond in silico prediction: multi-omics to identify a pathogenic deep intronic HNRNPK variant in Au-Kline syndrome.

Pathogenic variants in HNRNPK are associated with autosomal dominant Au-Kline syndrome (AKS, Au-Kline-Okamoto syndrome, OMIM #616580). This syndrome is characterized by developmental delay and intellectual disability, hypotonia, and distinctive facial features. Despite the use of whole-genome sequencing (WGS) as a powerful diagnostic tool, we nearly dismissed a novel intronic variant (NM_031263.4(HNRNPK):c.214-55 T > A) affecting HNRNPK splicing and function. Although commonly used bioinformatic splice prediction tools, including SpliceAI and PDIVAS, yielded inconclusive results, Face2Gene analysis indicated a high phenotypic similarity to AKS. Characteristic facial features described by Choufani et al. [1] supported the clinical diagnosis of AKS. Subsequent functional studies demonstrated aberrant splicing with intron retention, and DNA methylation profiling revealed a positive HNRNPK-specific episignature. These insights and the de novo status support an evaluation as likely pathogenic. This case report supports the relevance of facial analysis and comprehensive variant validation strategies, particularly for deep intronic variants with ambiguous in silico splicing predictions.

Journal Article↗

PubMed2026

Establishing a Multicenter Personalized Medicine Program in Childhood, Adolescent, and Young Adult Cancer in Spain: The SEHOP-PENCIL Project.

Pediatric cancer care in Spain lacked a national personalized medicine program. The SEHOP-PENCIL initiative, established by the SEHOP, was designed to address this gap. A national survey identified the genomic sequencing needs of hospitals treating pediatric patients with cancer. Results showed improved access to targeted next-generation sequencing panels but revealed persistent variability in implementation, limited availability of advanced sequencing (whole-exome sequencing, whole-genome sequencing, RNA sequencing, and DNA methylation profiling), and gaps in cancer predisposition clinics and molecular tumor boards (MTBs). SEHOP-PENCIL is organized as a network of 10 specialized genomic centers serving 45 hospitals through a centralized inclusion system. The program standardizes patient eligibility, genomic workflows, and result interpretation, supported by a national MTB. This framework enables informed clinical decision making, ensures access to molecular diagnosis and innovative therapies, and supports systematic data collection to advance pediatric cancer research and personalized care. SEHOP-PENCIL represents a pioneering national model for integrating precision oncology into pediatric cancer care in Spain. By fostering collaboration, standardizing genomic practices, and promoting equitable access, it aims to reduce disparities and improve outcomes, offering a scalable example for other decentralized health care systems.

Humans↗