EBioMedicine最新文献

{"title":"Early transcriptional responses following Ad26.COV2.S vaccination in individuals with prior SARS-CoV-2 infection.","authors":"Veronica V Rezelj, Jeroen Tolboom, Nina Hertoghs, Jan Serroyen, Mathieu Le Gars, Frank Struyf, Jenny Hendriks, Javier Ruiz Guiñazú, Chelsea McLean","doi":"10.1016/j.ebiom.2026.106270","DOIUrl":"https://doi.org/10.1016/j.ebiom.2026.106270","url":null,"abstract":"<p><strong>Background: </strong>Ad26.COV2.S is a recombinant, replication-incompetent human adenovirus serotype 26 (Ad26) vectored vaccine encoding a full-length SARS-CoV-2 spike protein in a prefusion-stabilised conformation. The genes and pathways which are differentially regulated following vaccination with Ad26.COV2.S, how these differ over time, and under different regimens, have not been investigated.</p><p><strong>Methods: </strong>Gene expression changes were profiled via RNAseq following the first and second dose of Ad26.COV2.S in a subset of individuals with pre-existing SARS-CoV-2 immunity due to prior SARS-CoV-2 infection, included in a randomised, double-blind, Phase 3 study (NCT#04908722). Transcriptional responses induced by a 1- and 2-dose regimen were assessed, each at two different dose levels: the marketed 5 × 10¹⁰vp dose level and a lower 1.25 × 10¹⁰vp dose level.</p><p><strong>Findings: </strong>Consistent with other vaccine studies, antiviral, interferon, cytokine, and monocyte blood transcriptional modules were differentially regulated one day post-Ad26.COV2.S vaccination. At three days post-vaccination, innate immunity was still transcriptionally active at lower levels than one day post-vaccination. By seven days post-Ad26.COV2.S, increased immunoglobulin gene expression dominated the transcriptome response, indicating a shift towards humoural and B cell responses and activation of adaptive immunity. Transcriptional responses post-Ad26.COV2.S were generally stronger after the first dose versus the second dose.</p><p><strong>Interpretation: </strong>In this study in whole blood, innate and adaptive immune transcripts were upregulated as early as one and seven days post-Ad26.COV2.S, respectively. These findings add to the limited data on innate immune responses to adenovirus-based vaccines in a clinical setting and contribute to understanding the mechanisms behind the adaptive immune responses that may contribute to protective immunity.</p><p><strong>Funding: </strong>This study was funded by Johnson & Johnson Innovative Medicine.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"127 ","pages":"106270"},"PeriodicalIF":10.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CT-based body composition and its change through time in relation to outcomes in participants screened for lung cancer.","authors":"Stijn Bunk, Edwin Bennink, Grigory Sidorenkov, Marjolein A Heuvelmans, Harry J M Groen, Hester A Gietema, Mathias Prokop, Joachim G Aerts, Colin Jacobs, Geertruida H de Bock, Pim A de Jong, Rozemarijn Vliegenthart, Firdaus Mohamed Hoesein","doi":"10.1016/j.ebiom.2026.106276","DOIUrl":"10.1016/j.ebiom.2026.106276","url":null,"abstract":"<p><strong>Background: </strong>Computed Tomography (CT) scans allow opportunistic evaluation of body composition. We investigated whether body composition and change through time are associated with lung cancer incidence and all-cause/lung cancer-specific mortality in a lung cancer screening cohort.</p><p><strong>Methods: </strong>A machine learning segmentation method was used in this retrospective cohort study to measure skeletal muscle area and density, and subcutaneous adipose tissue area (SAT) on repeated chest CTs from the Dutch-Belgian lung cancer screening trial. Hazard ratios by sex adjusted for age, smoking status, and smoking pack-years (aHR) were calculated for each outcome.</p><p><strong>Findings: </strong>During median follow-up of 12.2 (interquartile range, 1.2) years, 4.1% of 6187 subjects (85.5% male, mean age ± SD, 58.6 ± 5.5 years, smoking pack-years 41.2 ± 18.3) developed lung cancer, 12.2% died, and 2.1% died due to lung cancer. For males, SAT loss was associated with lung cancer incidence (aHR 1.19, 95% CI 1.02-1.39) and lung cancer-specific mortality (aHR 1.26, 95% CI 1.03-1.55), and less baseline muscle and muscle loss with all-cause mortality (aHR 1.20, 95% CI 1.10-1.31 and 1.17, 1.07-1.27). For females, less baseline SAT and SAT loss was associated with all-cause mortality (aHR 1.44, 95% CI 1.06-1.97 and 1.48, 1.13-1.94) and lung cancer-specific mortality (aHR 2.85, 95% CI 1.50-5.39 and aHR 1.96, 1.11-3.44). Models improved by including body composition trends for all-cause mortality (males: p < 0.001; females: p = 0.012) and for lung cancer-specific mortality (males: p = 0.102; females: p = 0.005).</p><p><strong>Interpretation: </strong>Body composition trends based on automated analysis of chest CT are associated with worse outcomes in participants screened for lung cancer.</p><p><strong>Funding: </strong>Dutch Cancer Society, Health Holland, Siemens Healthineers.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"127 ","pages":"106276"},"PeriodicalIF":10.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The polygenic score for age at menopause is independently associated with the response of controlled ovarian hyperstimulation in women undergoing IVF.","authors":"Charissa van Zwol-Janssens, Sander Lamballais, Elizabeth A Loehrer, Joop S E Laven, Tjitske Kleefstra, Yvonne V Louwers","doi":"10.1016/j.ebiom.2026.106267","DOIUrl":"10.1016/j.ebiom.2026.106267","url":null,"abstract":"<p><strong>Background: </strong>While Anti-Müllerian hormone (AMH) helps personalise In Vitro Fertilization (IVF) stimulation protocols, a significant number of women still do not achieve an optimal ovarian response. To address this, we explore the utility of a polygenic score for age at natural menopause (ANM) as a predictor for ovarian response during IVF.</p><p><strong>Methods: </strong>This cohort study included 435 women who underwent standardised IVF stimulation, and they were genotyped to calculate a polygenic score (PGS) for ANM. Linear regression and ANCOVA models were used to assess the associations between the PGS and ovarian response, oocyte and embryo quality and pregnancy rates, adjusting for genomic components and age.</p><p><strong>Findings: </strong>A one standard deviation increase in the PGS for ANM was associated with 0.950 (p < 0.001) additional follicles two days before ovum pick-up. While the PGS did not significantly associate with the overall diminished ovarian response (DOR), a mean difference of -0.33 (p < 0.01) in PGS was observed when comparing individuals with fewer than 8 follicles retrieved to those with an optimal ovarian response. No association was found between the PGS and ongoing pregnancy. Causal mediation revealed that the effect of the PGS onto the number of follicles was partly mediated by AMH levels (proportion mediated = 31%, p = 0.002).</p><p><strong>Interpretation: </strong>A lower PGS for ANM, indicative for earlier menopause, is independently associated with a reduced ovarian response during IVF stimulation, specifically fewer follicles retrieved and mostly independent of AMH levels. This highlights the potential of ANM-related genetic variants to inform personalised IVF protocols by predicting ovarian responsiveness.</p><p><strong>Funding: </strong>This study was supported by Ferring Pharmaceuticals.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"127 ","pages":"106267"},"PeriodicalIF":10.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-ancestry genome-wide association study of serum creatine kinase implicates myopathy genes and muscle pathways.","authors":"Gang Chen, Sizheng S Zhao, Hector Chinoy, James B Lilleker, Weijie Liu, Yuhui Li, Andrew P Morris, Janine A Lamb","doi":"10.1016/j.ebiom.2026.106274","DOIUrl":"10.1016/j.ebiom.2026.106274","url":null,"abstract":"<p><strong>Background: </strong>Serum creatine kinase (CK) is a routinely measured biomarker of muscle damage, yet the genetic factors underlying inter-individual variation in CK levels remain poorly defined.</p><p><strong>Methods: </strong>Here we present a large multi-ancestry genome-wide association meta-analysis of serum CK, comprising 237,255 participants spanning Admixed American, African American, East Asian, European and Middle Eastern populations.</p><p><strong>Findings: </strong>We identify 107 independent loci at genome-wide significance (P< 5 × 10^-8), 98 of which are previously unreported, with pronounced enrichment for genes expressed in skeletal and cardiac muscle and overlap with pathways related to muscle structure and function. Notably, eight loci map to genes implicated in Mendelian myopathies, underscoring a continuum from common regulatory variation to rare pathogenic mutations. Integrative quantitative trait locus (QTL)-based Mendelian randomisation and colocalisation implicate several genes in CK regulation, most prominently SMAD3, KLF5 and STAT3 within the transforming growth factor beta signalling pathway. CK levels show positive genetic correlations with traits reflecting tissue damage as well as muscle mass and strength, and negative correlations with C-reactive protein, indicating pleiotropic effects from muscle biology and enzyme clearance.</p><p><strong>Interpretation: </strong>These findings delineate the genetic architecture of serum CK across diverse populations and highlight muscle-related pathways contributing to CK variation.</p><p><strong>Funding: </strong>No funding was received for this study.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"127 ","pages":"106274"},"PeriodicalIF":10.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized, observer-blind, phase 1 study of immune responses to three human adenovirus type 26 vector-based vaccines.","authors":"Nina Hertoghs, Jan Serroyen, Jeroen Tolboom, Roy van Heesbeen, Nynke Ligtenberg, Sabrina Butler, Elizabeth Merrall, Mariska van Rosmalen, Ludo Lavreys, Maaike Maat-Ligthart, Chelsea McLean, Kerstin Luhn, Jenny Hendriks","doi":"10.1016/j.ebiom.2026.106271","DOIUrl":"10.1016/j.ebiom.2026.106271","url":null,"abstract":"<p><strong>Background: </strong>Adenovirus 26 (Ad26) vector-based vaccines have shown immunogenicity and safety in various infectious disease settings. However, the impact of each vaccine component (vector/insert) on the immune response has yet to be explored in a controlled setting across multiple vaccines.</p><p><strong>Methods: </strong>In this randomised, observer-masked, multicentre phase 1 study, participants aged 18-59 years were assigned to receive one of three vaccine regimens: Ad26.COV2.S (5 × 10¹⁰ viral particles [vp]), Ad26.RSV.PreF/Protein (1 × 10¹¹ vp + 150 μg RSV preF protein), or the Ad26.ZEBOV (5 × 10¹⁰ vp), MVA-BN-Filo (1 × 10⁸ InfU) vaccine regimen. The primary endpoint was the change in cytokines, chemokines, and other innate immune response mediators. Transcriptomics and proteomics analyses were also performed.</p><p><strong>Findings: </strong>From October 2022-August 2023, 160 participants received a study vaccine (Ad26.COV2.S, n = 66; Ad26.RSV.PreF/Protein, n = 48; Ad26.ZEBOV, n = 46). Median age was 35·5 years. All vaccines were well tolerated. Across vaccines, cytokine levels peaked on Day 2 and returned to baseline by Day 8. Highest geometric mean increases were observed with Ad26.RSV.PreF/Protein vaccine, followed by Ad26.COV2.S and Ad26.ZEBOV. The Ad26.RSV.PreF/Protein vaccine elicited the most differentially expressed genes and proteins, while Ad26.ZEBOV had the fewest. All vaccines induced strong innate responses associated with innate and antiviral immunity, hallmarked by interferons. Transcriptional responses were consistent among vaccines, differing primarily in magnitude rather than genes expressed.</p><p><strong>Interpretation: </strong>All three vaccine regimens induced specific immunogenic responses, were well tolerated, and triggered strong innate and antiviral immunity responses within 2 days post-vaccination, with no distinct immune signature observed across vaccines per transcriptomics/proteomics analyses.</p><p><strong>Funding: </strong>This study was funded by Johnson & Johnson.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"127 ","pages":"106271"},"PeriodicalIF":10.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shedding light on pain management: a translational systematic review of light therapy for the treatment of chronic pain.","authors":"Doriana Taccardi, Hailey G M Gowdy, Emily V Sharp, Prisha Adya, Tracy L Cupido, M Gabrielle Pagé, Nader Ghasemlou","doi":"10.1016/j.ebiom.2026.106251","DOIUrl":"https://doi.org/10.1016/j.ebiom.2026.106251","url":null,"abstract":"<p><strong>Background: </strong>Pharmacological options remain the primary approach for chronic pain management; however, alternative multimodal interventions are necessary. Light therapy, which can modulate circadian (24-h) rhythms, has been increasingly explored as a potential treatment for chronic pain; yet, its efficacy and underlying mechanisms remain unclear. This systematic review summarises evidence on photoreceptor-mediated light therapy for chronic pain in clinical and preclinical studies.</p><p><strong>Methods: </strong>Four databases (Ovid MEDLINE, EMBASE, PsycINFO, and Web of Science) were searched for studies published up to August 29, 2025. Eligible studies evaluated the effects of light therapy on chronic pain outcomes; risk of bias was assessed using the Cochrane tool for clinical populations and the SYRCLE tool for animal models. Studies involving light acting directly on the site of injury or skin were excluded. Outcomes related to pain were synthesised descriptively due to heterogeneity in study designs and interventions. This review was registered with the PROSPERO database (CRD42023429231).</p><p><strong>Findings: </strong>Of 7757 studies screened, 18 studies were included (11 clinical and 7 preclinical). Overall, light therapy was associated with improvements in pain-related outcomes. However, the findings were inconsistent, particularly when dim-light (low intensity illumination) conditions were used as controls. Evidence was limited by methodological heterogeneity, unclear risk of bias in most preclinical studies, and incomplete assessment of circadian rhythms.</p><p><strong>Interpretation: </strong>Light therapy may represent a promising non-pharmacological intervention for chronic pain. Current evidence is insufficient to draw firm conclusions regarding efficacy or underlying circadian mechanisms. Further well-designed studies incorporating circadian assessments and individual pain profiles are needed.</p><p><strong>Funding: </strong>This work was supported by the Canadian Institutes of Health Research (PJT-497592 and MYG-191676).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"106251"},"PeriodicalIF":10.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated spatial multi-omics delineates fatty acid degradation fuels malignant evolution at the tumour periphery in cervical squamous cell carcinoma.","authors":"Shitong Lin, Zhihui Luo, Yuting Li, Bai Hu, Minghan Qu, Binghan Liu, Canhui Cao, Ting Peng, Miaochun Xu, Yashi Xu, Xiaojie Liu, Xiaoli Wang, Li Li, Wencheng Ding, Zhenyu Xu, Ruizhi Li, Jingwei Zhao, Jingmin Zhang, Lingfang Wang, Fang Ren, Chaolong Wang, Peng Wu","doi":"10.1016/j.ebiom.2026.106256","DOIUrl":"10.1016/j.ebiom.2026.106256","url":null,"abstract":"<p><strong>Background: </strong>Cervical squamous cell carcinoma (CSCC) exhibits profound spatial heterogeneity in evolutionary trajectories across distinct tumour foci, yet the underlying mechanisms remain poorly understood.</p><p><strong>Methods: </strong>In this study, we performed an integrated spatial transcriptomic and metabolomic analysis of six CSCC and two normal cervical samples, supported by single-cell RNA sequencing (n = 20) and validated in an independent spatial enhanced resolution omics-sequencing cohort (n = 15), to map the spatial tumour architecture and cellular heterogeneity of CSCC. Findings were functionally confirmed using cell lines, patient-derived organoids, and mouse models.</p><p><strong>Findings: </strong>We identified that tumour foci with high spatial continuity demonstrated elevated cancer cell purity and exhibited distinct spatial stratification. The peripheral tumour foci (layer 3) exhibited enhanced proliferative capacity and aggressive traits characterised by elevated epithelial-to-mesenchymal transition (EMT) activity compared to core foci (layer 1), which correlated with advanced evolutionary states. A layer 3-specific gene signature predicted poorer overall survival in both the Cancer Genome Atlas (TCGA) and Tongji Hospital (TJH) cohorts. Spatial multi-omics uncovered progressive metabolic reprogramming along the core-to-periphery axis, with activation of fatty acid degradation emerging as a hallmark of layer 3 aggression. Genetic knockdown (HADH, HADHA and ECHS1) and pharmacological inhibition (mitotane and perhexiline) of fatty acid degradation attenuated malignant phenotypes of layer 3, including proliferation and EMT-driven invasion.</p><p><strong>Interpretation: </strong>Our work establishes spatially resolved activation of the fatty acid degradation as a key evolutionary engine fuelling the malignant phenotypes of peripheral tumour foci, and nominates stratification-targeted metabolic disruption as a spatially promising therapeutic strategy for CSCC.</p><p><strong>Funding: </strong>Noncommunicable Chronic Diseases-National Science and Technology Major Project (2025ZD0544100), National Natural Science Foundation of China (82372929, 82503148, 32300460, 32400555 and 82472696), China Postdoctoral Science Foundation (2025M772119), Hubei Provincial Natural Science Foundation (JCZRQN202500308).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"127 ","pages":"106256"},"PeriodicalIF":10.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the genetic aetiology of diabetes in Africa.","authors":"Alisha N Wade, Carolyn Padoa, Adebowale Adeyemo, Inês Barroso","doi":"10.1016/j.ebiom.2026.106265","DOIUrl":"https://doi.org/10.1016/j.ebiom.2026.106265","url":null,"abstract":"<p><p>Despite the high public health burden of diabetes in Africa, research into its genetic aetiology has been slow, limiting the continent's ability to benefit from an emerging era of diabetes precision medicine. Some progress is evident. In monogenic diabetes, where a molecular diagnosis enables tailored treatment, two cases from Africa successfully illustrate this approach despite the absence of routine affordable genetic testing, and control data from diverse African populations. Although limited, genome-wide association studies from African populations have discovered novel African-specific type 2 diabetes risk variants. Additionally, application of a type 1 diabetes genetic score helped define a novel type of insulin deficient non-autoimmune diabetes in sub-Saharan Africa. Multiple challenges remain, including interpretation of glycated haemoglobin, a frequently used diabetes biomarker, which is impacted by genetic variants common in the African continent. We review these issues, outline barriers to implementing diabetes precision medicine, and highlight areas for future development.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":" ","pages":"106265"},"PeriodicalIF":10.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Migrasome-mediated clearance of PLK4: a novel mechanism for centrosome homeostasis and tumor targeting.","authors":"Zitong Zhao, Yongmei Song","doi":"10.1016/j.ebiom.2026.106263","DOIUrl":"10.1016/j.ebiom.2026.106263","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"127 ","pages":"106263"},"PeriodicalIF":10.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translating brain anatomy and disease from mouse to human in latent gene expression space.","authors":"Chloe Jaroszynski, Mohammed Amer, Antoine Beauchamp, Jason P Lerch, Stamatios N Sotiropoulos, Rogier B Mars","doi":"10.1016/j.ebiom.2026.106259","DOIUrl":"10.1016/j.ebiom.2026.106259","url":null,"abstract":"<p><strong>Background: </strong>The mouse model is the most widely used animal model in neuroscience, yet translating findings to humans suffers from the lack of formal models comparing the mouse and the human brain. Here, we devised a framework using mouse and human gene expression to build a quantitative common space and apply it to models of neurodegenerative disease.</p><p><strong>Methods: </strong>We trained a variational autoencoder on mouse spatial transcriptomics, and embedded mouse and human gene orthologs in the model's latent space. We computed a latent cross-species similarity matrix for translation and compared translated maps to human ground truth evidence.</p><p><strong>Findings: </strong>We established the validity of our model based on anatomical homology. Independent of species, brain areas with similar latent patterns clustered together, improving the homology of known anatomical pairs, and preserving principles of brain organisation. Importantly, translating brain alterations in mouse disease models predicted human patterns of brain changes in Alzheimer's and Parkinson's diseases. We further determined the best mouse model for the AD patients, based on how well the translations matched the patient data, across multiple models and timepoints.</p><p><strong>Interpretation: </strong>Our work provides i) a quantitative bridge across evolutionary divergence between the human and the predominant preclinical species, ii) a predictive framework to help design and evaluate disease models. By highlighting which models are best suited across stages of disease, we effectively support the understanding of disease mechanisms, assist in the workflow of clinical trials, and ultimately accelerate the transformation of findings into improved human outcomes.</p><p><strong>Funding: </strong>Supported by the Biotechnology and Biological Sciences Research Council (BBSRC) UK, the Medical Research Council (MRC) UK, the European Research Council, and the NIHR Oxford Health Biomedical Research Centre.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"127 ","pages":"106259"},"PeriodicalIF":10.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}