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PubMed2026

Impact of Tumor Genomic Profile on Adjuvant Chemotherapy Efficacy in Resected Pancreatic Adenocarcinoma: Results From the PRODIGE-24/CCTG PA6 Study.

PURPOSE: Modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX/mFFX) is the standard adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC), offering survival benefits over gemcitabine (GEM). However, the contribution of molecular biomarkers to treatment selection remains unclear. Here, we characterize the molecular landscape of tumors from the PRODIGE-24/CCTG PA6 trial and assess the clinical impact of genomic alterations and molecular subtypes. PATIENTS AND METHODS: Tumor DNA sequencing was successfully performed in 317/350 tumors (168 mFFX; 149 GEM), complemented by transcriptomic subtyping using the PurIST classifier. Mutational status of four key PDAC driver genes and 24 homologous recombination repair (HRR)-associated genes was analyzed, alongside single-base substitution (SBS) mutational signatures. Primary and secondary end points were disease-free survival (DFS) and cancer-specific survival (CSS), respectively. RESULTS: In the mFFX group, the PurIST subtype was prognostic, with classical tumors showing superior DFS compared with basal-like tumors (stratified hazard ratio [sHR], 0.48 [95% CI, 0.31 to 0.77]). Among KRAS-mutated patients, mFFX significantly improved DFS compared with GEM (sHR, 0.60 [95% CI, 0.45 to 0.79]; P < .001), while no benefit was observed in KRAS wild-type tumors (interaction test, Pint. = 0.010). HRR and BRCA status were not predictive (Pint. = .568 and Pint. = .785, respectively). The benefit of mFFX was consistent across SBS-positive and SBS-negative subgroups. CONCLUSION: Overall, these results do not support a change in current adjuvant treatment strategies. mFFX remains the standard adjuvant regimen in PDAC, and the observed lack of benefit in KRAS wild-type tumors should be considered hypothesis-generating and warrants further investigation.

Humans↗

PubMed2026

Oncogenic PIK3CA reprograms glutamine metabolism to drive bladder cancer progression.

BACKGROUND: Genomic analysis has revealed that approximately 40% of bladder cancer (BLCA) tumors harbor alterations in the PI3K/AKT pathway, with PIK3CA mutations occurring in 15-25% of cases. PIK3CA, which encodes the catalytic p110α subunit of PI3K, plays a critical role in regulating cell survival, proliferation, and metabolism. However, the metabolic and functional consequences of PIK3CA mutations in BLCA remain poorly defined. METHODS: To investigate the role of PIK3CA mutations in BLCA, we performed targeted sequencing on tumors from patients, identifying recurrent alterations. Using CRISPR/Cas9 knock-in models in SCaBER and UM-UC-3 cell lines, we introduced the PIK3CA E545K mutation to study its effects. We conducted transcriptomic profiling, targeted metabolomics, and stable isotope tracing to assess metabolic reprogramming. Functional assays measured proliferation, mitochondrial complex I activity, and glutaminolysis. Orthotopic xenografts in mice were used to evaluate in vivo tumor growth and metabolism. RESULTS: PIK3CA mutations were present in 20% of cases, consistent with TCGA data. The E545K and E545Q hotspots accounted for 70% of these mutations. PIK3CA E545K strongly activated PI3K/AKT signaling. Transcriptomic analysis revealed enrichment of OXPHOS, fatty acid metabolism, and mTORC1 signaling. Metabolomics indicated changes in TCA cycle metabolites and enhanced reductive carboxylation of glutamine to citrate, driving fatty acid synthesis. Mutant cells showed increased expression of GLS1 and FASN, higher proliferation rates, and elevated mitochondrial complex I activity. In vivo, PIK3CA-mutant xenografts displayed significantly increased tumor growth. CONCLUSION: PIK3CA mutations are frequent drivers of metabolic reprogramming in BLCA, leading to increased glutamine flux, elevated OXPHOS activity, and enhanced fatty acid synthesis, all of which contribute to tumor progression. These findings provide the first comprehensive evidence that PIK3CA-driven metabolic alterations are both biomarkers of aggressive disease and actionable therapeutic targets. The efficacy of PI3Kα inhibition in combination with metabolic targets may support its potential in precision medicine for PIK3CA-mutant BLCA and highlights the value of integrating metabolic biomarkers into treatment strategies for advanced BLCA.

Journal Article↗

PubMed2026

Transposable elements as modulators of homoeologous gene expression in bread wheat: lessons from the pan-transcriptome era.

Bread wheat (Triticum aestivum L.) is an allohexaploid (AABBDD) whose three ancestral subgenomes generate complex patterns of gene regulation. Most genes exist as homoeologous triads, and the relative expression balance among copies, homoeolog expression bias, is central to polyploid evolution and adaptation. Recent high-quality assemblies, long-read transcriptomics, and pan-transcriptome resources have uncovered extensive cultivar-specific transcriptional diversity. Because transposable elements (TEs) compose over 80% of the wheat genome, they are prime candidates for shaping subgenome asymmetry. We synthesize recent pan-genomic and transcriptomic evidence, including genome-wide associations between TE insertions and genome-specific expression, and propose a unifying framework in which TEs modulate homoeolog expression by donating cis-regulatory sequences, altering chromatin states, producing small RNAs, and driving structural variation. We discuss experimental and computational challenges for establishing causality, and outline future functional and translational strategies to leverage TE-associated regulatory diversity in wheat breeding.

Triticum↗

PubMed2026

Blood Bile Acids for Inflammatory Bowel Disease Diagnosis and Disease Activity Assessment: A Metabolomics Meta-Analysis.

Alterations in circulating bile acids (BAs) have been reported in inflammatory bowel disease (IBD), but the consistency of these changes across clinically relevant comparisons remains unclear. Our goal was to investigate systemic BA alterations in IBD using a metabolomics meta-analysis with an exploratory analysis of BA-related gene expression as a supporting context. A systematic review and meta-analysis of 28 metabolomics studies examined blood BA profiles associated with IBD, IBD diagnosis, and disease activity assessment. Univariate analysis and logistic regression modeling of two independent IBD cohorts explored the blood BA-related genes and IBD. Across 28 studies that comprised 5056 IBD patients, 1721 healthy controls, and 314 non-IBD patients, 131 BAs were reported. Eight predefined clinical comparisons were eligible for the meta-analysis. Lower secondary BA levels were consistently observed in IBD patients compared with controls, between UC and CD, and in active versus remission patients. Deoxycholic acid, glycodeoxycholic acid, and taurodeoxycholic acid were frequently decreased, whereas glycocholic acid was increased in certain comparisons. Transcriptomics analyses revealed differential expression of several BA-related genes in blood, including SLC51A, ABCB4, and ACOT8, across the comparisons. Our findings identify consistent circulating BA alterations in IBD and highlight the relevance of blood BA for future biomarker research in the diagnosis and disease activity assessment.

Humans↗

PubMed2024

The Genetic Determinants and Genomic Consequences of Non-Leukemogenic Somatic Point Mutations.

Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as point mutations or mosaic chromosomal alterations (mCAs) in genes associated with hematologic malignancy, are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions. To characterize CH without known driver genetic lesions, we used 51,399 deeply sequenced whole genomes from the NHLBI TOPMed sequencing initiative to perform simultaneous germline and somatic mutation analyses among individuals without leukemogenic point mutations (LPM), which we term CH-LPMneg. We quantified CH by estimating the total mutation burden. Because estimating somatic mutation burden without a paired-tissue sample is challenging, we developed a novel statistical method, the Genomic and Epigenomic informed Mutation (GEM) rate, that uses external genomic and epigenomic data sources to distinguish artifactual signals from true somatic mutations. We performed a genome-wide association study of GEM to discover the germline determinants of CH-LPMneg. After fine-mapping and variant-to-gene analyses, we identified seven genes associated with CH-LPMneg (TCL1A, TERT, SMC4, NRIP1, PRDM16, MSRA, SCARB1), and one locus associated with a sex-associated mutation pathway (SRGAP2C). We performed a secondary analysis excluding individuals with mCAs, finding that the genetic architecture was largely unaffected by their inclusion. Functional analyses of SMC4 and NRIP1 implicated altered HSC self-renewal and proliferation as the primary mediator of mutation burden in blood. We then performed comprehensive multi-tissue transcriptomic analyses, finding that the expression levels of 404 genes are associated with GEM. Finally, we performed phenotypic association meta-analyses across four cohorts, finding that GEM is associated with increased white blood cell count and increased risk for incident peripheral artery disease, but is not significantly associated with incident stroke or coronary disease events. Overall, we develop GEM for quantifying mutation burden from WGS without a paired-tissue sample and use GEM to discover the genetic, genomic, and phenotypic correlates of CH-LPMneg.

Journal Article↗

PubMed2026

Systemic immune activation in hereditary cancer predisposition syndromes: a cross-sectional study.

BACKGROUND: Immune surveillance mechanisms contribute to the elimination of precancerous lesions in hereditary cancer predisposition syndromes (HCPSs). METHODS: By combining single-cell transcriptomics, multiparametric mass cytometry and cytokine profiling of the systemic immune environment in 391 individuals among whom 227 are living with HCPSs we investigated phenotypic alterations in cancer-free individuals with HCPS. RESULTS: A decrease in peripheral B cell abundance and their more differentiated phenotype have been confirmed both in breast cancer patients with germline pathogenic variants in BRCA1 (gpath(BRCA1)) and in patients living with Lynch syndrome (LS). Pre-cancer women with gpath(BRCA1) exhibited an activated phenotype of multiple immune cell lineages, similar to those with manifest disease. In LS, B cell phenotypes exhibited the largest changes in response to cancer eradication, while increased peripheral IL-6 levels was detected even in presymptomatic individuals with LS. CONCLUSIONS: HCPS-specific differences in the phenotype of the systemic immune system might be leveraged in future risk-reducing strategies.

Humans↗

PubMed2026

Cell-of-origin Discovery in Infant Leukemia through Integration of 3D Models and Patient Transcriptomic Data.

Pediatric hematological malignancies remain challenging to investigate and model due to the age group-specificity of certain genetic abnormalities. In utero origin has been demonstrated for a subset of pediatric leukemias, placing their respective cell of origin (CoO) during embryonic development. We recently reported a 3D hemogenic gastruloid (haemGx) model of embryonic blood formation derived from mouse embryonic stem cells, resolving the spatio-temporal complexity of developmental hematopoiesis. Importantly, it allows genetic engineering to introduce disease-relevant mutations. Using haemGx, we modeled the most common acute myeloid leukemia exclusive to infants (infAML), subtype t(7;12)(q36;p13), which arises in utero and is characterized by MNX1 overexpression. Here, we detail a method to define susceptibility to specific mutations that integrate phenotypic and transcriptional changes in the haemGx system and compares them with patient data. By proxy of our MNX1-overexpression haemGx, we show a pipeline from cell engineering to downstream analyses of leukemogenic potential. In particular, we focus on the clinical relevance of the model by integrating single-cell and/or bulk RNA sequencing from the haemGx platform with patient data to extract cellular composition and temporal placement of the putative CoO. This method is adaptable to the introduction of other oncogenic mutations, chromosomal rearrangements, or epigenetic modifications, as well as to chemical perturbations, including drug vulnerability and growth factor dependence. This flexibility allows for broad application across diverse disease contexts, enabling mechanistic dissection of how specific alterations disrupt early developmental trajectories with clinical relevance.

Humans↗

PubMed2026

Identification of potential key genes involved in iron deficiency for sepsis: A retrospective cohort and transcriptomic study.

Iron overload has been associated with sepsis, but the role of iron deficiency and its molecular links remain unclear. We investigated the association between iron deficiency and sepsis and identified candidate genes potentially linking these conditions. MIMIC-IV data were used to assess the association between serum iron and sepsis status. Transcriptomic datasets from dietary iron-deficient mice (GSE10421), LPS-induced septic mice (GSE267388), and a human blood sepsis cohort (GSE137340) were sequentially analyzed to identify and externally evaluate candidate genes. IEU Open GWAS summary statistics were used for exploratory Mendelian randomization (MR). Exploratory drug prediction was performed using L1000FWD, followed by molecular docking analysis. Patients with sepsis had significantly lower serum iron levels, and restricted cubic spline analysis showed a nonlinear association between serum iron and the odds of sepsis. Cross-tissue transcriptomic analysis identified Sqle, Lss, and Rdh11 as candidate genes. In the human blood cohort, SQLE and RDH11 were significantly increased, whereas LSS was not significantly altered. Exploratory MR showed that genetically proxied SQLE expression was associated with higher odds of sepsis (odds ratio [OR] = 1.23, P = 1.67 × 10-3), whereas LSS expression was associated with lower odds (OR = 0.97, P = 8.90 × 10-4); RDH11 showed no significant association (OR = 1.01, P = .90). Drug prediction identified ML106 as the top-ranked candidate drug, and molecular docking predicted potential binding poses with SQLE and LSS. Serum iron showed a nonlinear association with sepsis status. SQLE, LSS, and RDH11 emerged as candidate genes, with concordant expression changes of SQLE and RDH11 observed in human blood. MR findings for SQLE and LSS were exploratory and require further validation. ML106 was identified through exploratory drug prediction and requires experimental validation before its therapeutic relevance can be established.

Sepsis↗

PubMed2026

Transcriptomic Profiling of Canine Testicular Leydig Cell Tumors Uncovers Key Upregulated Gene Pathways.

Total RNA was isolated from sections of healthy testes and Leydig cell tumors of mixed-breed dogs using TMA Master II device. The RNA-seq libraries were sequenced on the Illumina platform. Following differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were applied with quality control obtained using FastQC and Trimmomatic. This analysis revealed 1500 transcripts, including 928 upregulated and 168 downregulated genes. The results demonstrated that a significant proportion of these differentially expressed genes are directly involved in the control of sex steroid production (CYP11A1, STAR, and 3β-HSD3B1) or tube formation, angiogenesis, and extracellular matrix remodeling in interstitial cells (ESM1, FGG, and VEGFA). Moreover, we identified the upregulation of transcripts responsible for neurotransmitter or neuroendocrine signaling (SLC6A4, GRIN2C, GABRB3) and cholesterol metabolism and its regulation (GPX3, MSMO1, DHCR24). These genes were strongly associated with the phosphatidylinositol-3-kinase (PI3K)-Protein Kinase B (Akt) cascade and extracellular matrix interactions, features shared with various malignancies. Alterations in estrogen and relaxin signaling appear to be distinctive, understudied mechanisms specific to canine Leydig cell tumors. Concurrently, downregulated genes (e.g., DMRTC2, SEMA3C, ALOX12) were linked with cell differentiation, signaling and immunoregulatory pathway suppression involved in tumorigenesis. A complex transcriptomic profile of canine Leydig cell tumors was developed, revealing a conserved oncogenic core shared in some aspects with human malignancies alongside unique species-specific alterations. Findings seem to be useful for identifying novel diagnostic biomarkers and targeted therapies in veterinary oncology, establishing canine reproductive tissues as a valuable comparative biomedical model for research in human.

Leydig cell tumor↗

PubMed2026

Multiomics profiling of plasma reveals lipid-immune dysregulation and exosome remodeling in mpox and mpox-HIV co-infection.

BACKGROUND: Monkeypox virus (MPXV) infects diverse human cell types, and human immunodeficiency virus (HIV) co-infection is common. The immunometabolic consequences of MPXV infection, and how it may be altered by HIV, remain poorly defined. METHODS: We performed quantitative plasma lipidomics and precise metabolomics in a discovery cohort (n = 81) comprising MPXV-monoinfected (MPLWOH), MPXV-HIV-coinfected (MPLWH), and HIV-monoinfected (PLWH) patients and healthy controls, integrating exosome proteomics, cytokine profiling, and transcriptomics of exosome-treated HepG2 and A549 cells for functional interpretation. An independent validation cohort (n = 65) was used to assess cross-cohort reproducibility. FINDINGS: MPXV infection induced broad lipid remodeling, with elevations in phosphatidylserine (PS) and phosphatidylethanolamine (PE) and reductions in phosphatidylcholine (PC), lysophospholipids, cholesteryl ester (CE), and exosomal lecithin-cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL). These lipid alterations were correlated with tissue injury markers and inflammatory cytokines. The MPLWH group exhibited more severe metabolic disruption, including marked sulfatide (SL) depletion, lower cholesterol and high-density lipoprotein cholesterol (HDL-c), and extensive rewiring of lipid-cytokine associations. SL depletion in MPLWH correlated with abundances of COPI-mediated retrograde trafficking proteins in exosomes. Transcriptomic profiling of exosome-treated cells provided functional validation: MPLWOH exosomes induced lipid metabolism and repair-associated epithelial programs, while MPLWH exosomes drove phospholipid remodeling and acute inflammatory and mucosal barrier-stress responses. CONCLUSIONS: MPXV infection reprograms host lipid metabolism and exosome composition, with HIV co-infection amplifying inflammatory, metabolic, and trafficking disruptions. These convergent multi-omics signatures link systemic lipid dysregulation to exosome-mediated immunomodulation and identify potential targets for host-directed interventions. FUNDING: This study was funded by the Major Project of Guangzhou National Laboratory.

Adult↗

PubMed2025

Multi-omics technologies: Novel tools and methods for assessing nerve injury and regeneration.

Recently, with the rapid advancement of multi-omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, new tools and approaches have been introduced for studying nerve injury and regeneration. This review highlights the application and progress of multi-omics in uncovering the mechanisms of nerve injury, guiding the development of regenerative strategies, and promoting clinical translation. By integrating multi-omics datasets, researchers can comprehensively track dynamic molecular changes following nerve injury, including abnormal gene expression, disrupted protein signaling, altered metabolic programs, and shifts in the immune microenvironment. Single-cell multi-omics technologies resolve cellular heterogeneity, revealing the distinct functions of neurons, glial cells, and immune cell subpopulations during the injury response. Spatially resolved transcriptomics maintain the spatial context of lesion and regeneration sites, enabling precise localization for targeted interventions. Multi-omics technologies not only identify key molecular players involved in nerve regeneration but also create opportunities for personalized medicine. Nonetheless, integrating multi-omics data poses technical challenges, including high dimensionality, batch effects, and algorithmic constraints, while ethical concerns related to stem cell therapy and gene editing require stringent oversight. To transition from structural reconstruction to functional remodeling, future research should emphasize artificial intelligence-driven data integration, organ-on-a-chip modeling, and cross-disciplinary collaboration to overcome existing technical barriers and accelerate the clinical application of neuroregenerative therapies.

artificial intelligence↗

PubMed2026

Exploring the transcriptional crosstalk between adipose tissue and locoregional recurrence in breast cancer using independent component analysis.

Locoregional recurrence (LRR) poses a persistent clinical challenge in breast cancer, with emerging evidence implicating the tumor-associated adipose tissue in modulating recurrence risk. This study investigates shared transcriptional programs between adipose tissue and breast tumors and examines their association with disease-free survival (DFS), particularly in the context of reconstructive surgery where adipose tissue from different body compartments are commonly used. We analyzed bulk gene expression data from 5,691 breast tumors and 978 human adipose tissue samples from different body compartments using consensus-independent component analysis (c-ICA) to identify transcriptional components (TCs). Gene set enrichment analysis (GSEA) and copy number alteration profiling were used for biological annotation. Associations between TCs and DFS were evaluated through univariate Cox regression. Key findings were validated using spatial transcriptomic and single-cell RNA sequencing datasets. Among the 411 TCs identified, 332 showed biological enrichment, and 35 were significantly associated with DFS. Four DFS-associated TCs (TC257, TC350, TC371, TC400) were enriched for adipogenesis-related genes and exhibited heightened activity in high-grade, triple-negative tumors and in patients with elevated BMI. Notably, TC350 was highly active in adipose tissue from common reconstructive donor sites (abdomen, omentum, subcutis) but not in native breast adipose tissue. Spatial transcriptomic and single-cell analyses confirmed the increased activity of these adipogenesis-related TCs in tumor regions and adipose cells. TC350 included FABP4, a gene previously linked to poor prognosis in breast cancer and considered as a potential new therapeutic target. Adipose tissue-derived transcriptional programs influence breast cancer prognosis and this seems to differ by tissue origin. These findings generate a hypothesis that donor site selection for adipose tissue in reconstructive surgery may impact LRR risk through adipogenesis-associated mechanisms. Further research is warranted to elucidate the biological and clinical implications of adipose-tumor transcriptional interactions.

Humans↗

PubMed2025

Intrinsic changes in cell differentiation and identity drive impaired wound healing in aged female murine skin.

Cellular and molecular mechanisms that drive a perturbed wound microenvironment and impaired healing in aged skin have not been fully delineated. To obtain a comprehensive understanding of cell-intrinsic changes acquired during ageing that impact early responses to injury, we performed single-cell RNA sequencing in young and aged intact female murine skin and wounds 3 days post-injury. We observed that substantial changes in the mean proportional distribution and transcriptomic state of skin resident subpopulations in aged, but not young, tissues accompany a global increase in basal inflammation. This is driven by an altered signalling environment leading to impaired keratinocyte differentiation, loss of fibroblast identity and defective macrophage function. Further, we show that ageing-induced changes in skin resident cells persist after injury, resulting in increased expression of senescence-related genes in wound fibroblasts and aberrant monocyte-to-macrophage transitioning coupled to an enhanced inflammatory signature and defective intercellular signalling in comparison to wounds in young mice. In summary, our data highlights a contribution of both cell-intrinsic changes and an altered tissue microenvironment to poor wound healing responses in aged mice.

Animals↗

PubMed2025

Tissue tropism, pathology, and pathogenesis of West Nile virus infection in saltwater crocodile (Crocodylus porosus).

West Nile virus (WNV) is one of the leading causes of economic losses to the saltwater crocodile farming industry due to skin lesions, known as "pix", induced by the infection. Our previous study suggested a possible immunopathological pathway causing these lesions. We therefore resolved to investigate the kinetics of WNV-infection and the elicited immune responses in experimentally challenged saltwater crocodile hatchlings. Employing virus isolation, quantitation of viral genome loads in tissues by RT-qPCR and immunohistochemistry, we demonstrated that upon infection, the virus replicates in the spleen, liver and later in the pancreas. Transcriptomic analysis, based on RNA sequencing and RT-qPCR of kidney and liver tissues, revealed that the early host response is primarily via alteration of cellular structure and metabolism. As the infection progresses, the response becomes predominantly inflammatory and antiviral. The results suggest that the kidney and gastrointestinal tract are primary nidi of viral replication leading to cloacal shedding, but a link to skin lesion development remains to be fully clarified.

Animals↗

PubMed2025

Exploring phage-host interactions in Burkholderia cepacia complex bacterium to reveal host factors and phage resistance genes using CRISPRi functional genomics and transcriptomics.

Complex interactions of bacteriophages with their bacterial hosts determine phage host range and infectivity. While phage defense systems and host factors have been identified in model bacteria, they remain challenging to predict in non-model bacteria. In this paper, we integrate functional genomics and transcriptomics to investigate phage-host interactions, revealing active phage resistance and host factor genes in Burkholderia cenocepacia K56-2. Burkholderia cepacia complex species are commonly found in soil and are opportunistic pathogens in immunocompromised patients. We studied infection of B. cenocepacia K56-2 with Bcep176, a temperate phage isolated from Burkholderia multivorans. A genome-wide dCas9 knockdown library targeting B. cenocepacia K56-2 was constructed, and a pooled infection experiment identified 63 novel genes or operons coding for candidate host factors or phage resistance genes. The activities of a subset of candidate host factor and resistance genes were validated via single-gene knockdowns. Transcriptomics of B. cenocepacia K56-2 during Bcep176 infection revealed that expression of genes coding for host factor and resistance candidates identified in this screen was significantly altered during infection by 4 h post-infection. Identifying which bacterial genes are involved in phage infection is important to understand the ecological niches of B. cenocepacia and its phages, and for designing phage therapies.IMPORTANCEBurkholderia cepacia complex bacteria are opportunistic pathogens inherently resistant to antibiotics, and phage therapy is a promising alternative treatment for chronically infected patients. Burkholderia bacteria are also ubiquitous in soil microbiomes. To develop improved phage therapies for pathogenic Burkholderia bacteria, or engineer phages for applications, such as microbiome editing, it's essential to know the bacterial host factors required by the phage to kill bacteria, as well as how the bacteria prevent phage infection. This work identified 65 genes involved in phage-host interactions in Burkholderia cenocepacia K56-2 and tracked their expression during infection. These findings establish a knowledge base to select and engineer phages infecting or transducing Burkholderia bacteria.

Bacteriophages↗

PubMed2026

Polystyrene microplastics induce auditory neurotoxicity in mammals: Integrated multi-omics profiling reveals oxidative damage and synaptic molecular dysregulation.

Microplastics (MPs) are ubiquitous environmental pollutants, yet their neurotoxic effects on the auditory system remain poorly understood. This study develops an integrated multi-level analytical framework combining auditory neurophysiology, behavioral assessment, tissue biochemistry, transcriptomics, and proteomics to investigate polystyrene (PS)-MPs-induced auditory neurotoxicity in rats. PS-MPs infiltrate the auditory system and significantly impair auditory processing, with central dysfunction emerging earlier and more prominently than peripheral alterations. Multi-omics analyses reveal coordinated suppression of glutamatergic synapse and Wnt signaling pathways in the cochlear nucleus. Mechanistically, PS-MPs perturb the crosstalk between glutamatergic synaptic and Wnt signaling, promoting AMPA receptor (AMPAR) internalization and potentially affecting synaptic plasticity-related processes and neuronal responsiveness. In parallel, PS-MPs trigger oxidative stress, apoptosis, and glial activation, reflecting pronounced neuroinflammatory and redox imbalance. In primary cochlear nucleus neurons (PCNNs), these mechanisms were further validated in vitro, where activation of Wnt signaling by Wnt3a significantly alleviated oxidative injury and reduced AMPAR internalization. Collectively, these findings provide comprehensive preclinical evidence for the neurotoxic potential of MPs and reveal a previously unrecognized PS-MPs-induced auditory neurotoxicity, although further studies are needed for human relevance. Results from the rat model further implicate Wnt-mediated signaling as a potential modulatory pathway underlying MPs-induced synaptic molecular alterations and redox dysfunction.

Animals↗

PubMed2026

Integration of multi-omics data uncovers novel germline susceptibility candidates in early-onset colorectal cancer.

Colorectal cancer (CRC) is increasingly diagnosed in individuals under 50 years of age, yet the underlying genetic predisposition remains largely unexplained, particularly in mismatch repair (MMR)-proficient cases. This study aimed to identify novel hereditary CRC susceptibility genes by integrating germline and tumour whole-exome sequencing (WES) with transcriptomic profiling across a cohort of early-onset CRC (EOCRC) patients. Tumours were categorised using Consensus Molecular Subtypes (CMS) classification and analysed for mutational signature and burden. We used a novel 'All vs One' multi-omic integration approach to identify loss-of-function rare germline variants with concordant gene expression alterations in tumour tissue. Five candidate genes (ADCY4, NOXO1, CDHR2, ARHGAP10, EEF2K) were prioritised based on this approach and potential biological relevance in CRC. These findings highlight the molecular heterogeneity of EOCRC and demonstrate the utility of multi-omic approaches in refining germline variant interpretation. Integrating tumour transcriptomics enhances gene discovery efforts and supports a more comprehensive understanding of CRC heritability in younger individuals.

Humans↗

PubMed2026

Changes of DNA methylation and gene expression profile in placental villi and chorioamniotic membranes under preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious pregnancy complication with elusive pathogenesis. Although epigenetic dysregulation is implicated, its layer-specific placental roles are poorly defined. This study aimed to identify shared and layer-specific epigenetic alterations in PE by profiling DNA methylation and gene expression in placental villi (PV) and chorioamniotic membranes (CAM). RESEARCH DESIGN AND METHODS: PV and CAM samples were collected from 7 normal and 8 PE pregnancies, and three public DNA methylation datasets (GSE98224, GSE44667, GSE75196) were integrated. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified based on whole-genome methylation and transcriptome sequencing. Layer-specific and shared gene sets were identified by cross-analysis, with functional annotation using Gene Ontology (GO). RESULTS: EM-seq revealed a hypermethylation-dominant, tissue-specific methylation landscape in PE placentas. Cross-tissue comparison identified shared DMGs between the two layers, including nine key genes consistently altered in public datasets. Integrated analysis in PV further identified 22 co-dysregulated genes, enriched in thermoregulation, maternal-fetal immunity, signal transduction, and cell differentiation. CONCLUSIONS: This study elucidates the shared and layer-specific dysregulation of gene networks at methylomic and transcriptomic levels in PE placenta. Comparing PV and CAM highlights placental epigenetic heterogeneity and dysfunction, offering novel clues for mechanistic research and layer-targeted therapies.

Humans↗