Genome Medicine最新文献

{"title":"The contribution of rare germline variants to the immune landscape of breast cancer.","authors":"Felipe Rojas-Rodríguez, Sander Canisius, Renske Keeman, Aaron J Bernstein, Amber N Hurson, Thomas U Ahearn, Irene L Andrulis, Antonis C Antoniou, Sabine Behrens, Katarzyna Białkowska, Fiona M Blows, Manjeet K Bolla, Nicola J Camp, Melissa H Cessna, Jenny Chang-Claude, Stephen J Chanock, Joe Dennis, Peter Devilee, Alison M Dunning, Jacek Gronwald, Ute Hamann, Antoinette Hollestelle, Maartje J Hooning, Hugo M Horlings, Agnes Jager, Anna Jakubowska, Brandt Jones, Rudolf Kaaks, Marleen Kok, Jolanta Lissowska, Jan Lubiński, Mehdi Manoochehri, Jodi L Miller, Noor Muhammad, Anna Marie Mulligan, Nadia Obi, Muhammad U Rashid, Hans-Peter Sinn, Carolien H M van Deurzen, Qin Wang, Justin A Williams, Xiaohong R Yang, Douglas F Easton, H Raza Ali, Montserrat García-Closas, Paul D P Pharoah, Mustapha Abubakar, Marjanka K Schmidt","doi":"10.1186/s13073-026-01662-6","DOIUrl":"https://doi.org/10.1186/s13073-026-01662-6","url":null,"abstract":"<p><strong>Background: </strong>Many breast cancer predisposition genes are involved in DNA damage repair, leading to genome instability that can impact immunosurveillance, neoantigen formation, and the composition of the tumor immune microenvironment.</p><p><strong>Methods: </strong>Here, we explored associations between germline protein truncating variants (PTVs) in 34 (putative) breast cancer predisposition genes, of which 26 involved in DNA damage repair, with the abundance of four immune cell markers, i.e., CD8 + , FOXP3 + , CD20 + and CD163 + , across 7,969 invasive breast tumors of women of European ancestry.</p><p><strong>Results: </strong>The most apparent associations were those of CD163, a marker of M2-like tumor-associated macrophages, with genes involved in double- and single-strand break DNA repair, and with the 12 known breast cancer predisposition genes combined. Specifically, DNA damage repair genes, BRCA1, BRCA2, PALB2, RAD51D, and MSH6 were associated with a 1.3 to twofold abundance of CD163-positive cells. Estrogen receptor status was found to mediate associations to a limited extent.</p><p><strong>Conclusions: </strong>Our findings support a role of rare pathogenic germline variants involved in DNA damage repair, and particularly those predisposing to breast cancer, in the immune landscape of breast tumors. These insights may help guide the development of immunomodulatory strategies for breast cancer prevention and treatment.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"African ancestry and risk variants associated with triple-negative breast cancer susceptibility in African American women.","authors":"Guochong Jia, Lili Liu, Jie Ping, Peter N Fiorica, Xingyi Guo, Ran Tao, Bingshan Li, Jian Gu, Esther M John, Olufunmilayo I Olopade, Michael F Press, Abenaa M Brewster, Andrew F Olshan, Gary Zirpoli, Ebonee N Butler, Maosheng Huang, Dezheng Huo, Julie R Palmer, Christopher A Haiman, Christine B Ambrosone, Melissa A Troester, Jirong Long, Song Yao, Wei Zheng","doi":"10.1186/s13073-026-01665-3","DOIUrl":"https://doi.org/10.1186/s13073-026-01665-3","url":null,"abstract":"<p><strong>Background: </strong>Compared to European American women, African American women are more likely to be diagnosed with triple-negative breast cancer (TNBC). This difference may be partially due to genetic factors. This study aims to investigate associations of African ancestry and risk variants with TNBC among African American women.</p><p><strong>Methods: </strong>We used data from 2,335 TNBC cases, 8,159 estrogen receptor (ER)-positive cases, and 9,814 controls included in the African-ancestry Breast Cancer Genetics (AABCG) Consortium. The proportion of African ancestry (%AFR) and local ancestry were estimated using samples from the 1000 Genomes Project as reference. Logistic regressions were performed for case-control (TNBC vs. control) and case-case (TNBC vs. ER-positive) comparisons, adjusted for age, study, genotype principal components 2-5, body mass index, and reproductive factors. Local ancestry-aware association analyses were conducted in 12 TNBC risk loci to identify ancestry-specific risk variants.</p><p><strong>Results: </strong>In case-control analyses, no statistically significant association was found between %AFR and TNBC risk after adjustment for potential confounders. However, TNBC cases had a significantly higher mean % AFR (mean = 0.811, standard deviation, SD = 0.104) compared to ER-positive cases (mean = 0.798, SD = 0.110, P < 0.001). Females with %AFR of ≥ 95% had 1.62 times higher odds (95% confidence interval, CI: 1.16-2.25) of having TNBC rather than ER-positive breast cancer, compared to those with %AFR of 55.0-64.9%. Local ancestry-aware association analyses identified seven subtype-informative variants in or near MDM4, RP11-19E11.1, TERT, MRPL36, TCF7L2, C11orf65, and ANKLE1. All of them were significantly associated with TNBC as compared with ER-positive cases, and six of them were also associated with TNBC risk in case-control analyses. Large allelic odds ratios of 1.25 or higher were found in association with TNBC risk or subtype classification. The risk allele frequency for five of them is substantially higher in haplotypes of African ancestry than those of European ancestry.</p><p><strong>Conclusions: </strong>These findings support a significant role of African-ancestry specific genetic factors in determining breast cancer subtypes and highlight the need for future research to uncover possible pathways driving TNBC susceptibility.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival Genie 2: a next-generation web server for targeted and single-cell-based survival analyses.","authors":"Chenbin Huang, Marina E Michaud, Hope Mumme, Swati S Bhasin, Manoj K Bhasin","doi":"10.1186/s13073-026-01651-9","DOIUrl":"https://doi.org/10.1186/s13073-026-01651-9","url":null,"abstract":"<p><strong>Background: </strong>With the growing number of publicly available cancer genomics datasets, numerous web-based survival analysis tools have been developed to link gene expression data with patient outcomes, aiming to discover novel biomarkers and therapeutic targets. However, existing tools primarily support single-gene or gene-set analyses catered to targets derived from traditional sequencing approaches, limiting their applicability in the era of single-cell genomics.</p><p><strong>Results: </strong>Here, we introduce Survival Genie 2, the first web-based platform uniquely designed to facilitate survival analyses integrating user-generated single-cell data. Through this novel approach, our tool enables researchers to identify outcome-associated genes from single-cell cluster markers and weighted gene co-expression network modules. Furthermore, Survival Genie 2 offers specialized capabilities for parsing user inputs into biologically relevant categories, including long noncoding RNAs (lncRNAs), transcription factors, and ligand-receptor signaling genes, enhancing the robustness and interpretability of survival associations. Importantly, Survival Genie 2 also hosts the most comprehensive database to date, comprising 132 datasets from 53 cancer genome projects across 38 distinct malignancies, including both adult and pediatric cancers. The tool further provides versatile partitioning methods, generating analysis results through univariate Cox proportional hazards modeling, which are presented in publication-ready Kaplan-Meier and integrated forest plots. Additionally, Survival Genie 2 uniquely bridges the gap between publicly available bulk sequencing datasets and cell-type-specific targets derived from the user's single-cell sequencing data by correlating user input gene expression with predicted immune cell enrichment, estimated through deconvolution analysis on the selected cancer dataset.</p><p><strong>Conclusions: </strong>By integrating these innovative features, with specialized survival analyses on single-cell cluster markers, co-expression modules, regulatory networks, and ligand-receptor pairs, Survival Genie 2 represents a novel tool for expanding the translational impact of cancer research, enabling the precise identification of biomarkers and therapeutic targets. Survival Genie 2 is available at https://bhasinlab.bmi.emory.edu/SurvivalGenie2/home.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive molecular characterization identifies therapeutic vulnerabilities in ovarian clear cell carcinoma.","authors":"Yong Wu, Xinyi Guo, Tiantian Wang, Tianyi Zhao, Siyu Chen, Ying Su, Qin Li, Jun Zhu, Lingfang Xia, Xingzhu Ju, Xiaohua Wu, Shenglin Huang, Zhixiang Hu, Xiaojun Chen","doi":"10.1186/s13073-026-01663-5","DOIUrl":"https://doi.org/10.1186/s13073-026-01663-5","url":null,"abstract":"<p><strong>Background: </strong>Ovarian clear cell carcinoma (OCCC) is a rare aggressive, and chemo-resistant subtype of epithelial ovarian cancer. Current limitations in precisely characterizing its molecular features have resulted in restricted availability of clinical targeted therapies and significant therapeutic challenges.</p><p><strong>Methods: </strong>To address this unmet need, we conducted an integrative multi-omics study of 82 OCCC cases, incorporating whole-exome sequencing (WES), bulk RNA sequencing, and single-cell RNA sequencing (scRNA-seq).</p><p><strong>Results: </strong>Our analysis uncovered recurrent mutations in multiple epigenetic regulators including ARID1A, EP300, and SETD2B, reinforcing chromatin remodeling as a hallmark of OCCC pathogenesis. Strikingly, FOXA2 mutations were absent in early-stage tumors but specifically enriched in advanced-stage cases (19% frequency), with functional validation demonstrating their role in driving malignant progression. Copy number alteration profiling revealed frequent amplifications in chromosomal arms such as 17q, which contains the ERBB2 oncogene that potentially regulates OCCC progression. Chromosomal translocations were detected in 35.59% of cases, including a novel FGFR2/RPAP3 fusion with therapeutic implications. Notably, scRNA-seq delineated immune-rich subsets characterized by abundant cytotoxic T-cell and B-cell infiltration, suggesting immunotherapeutic opportunities in a patient subset. Moreover, molecular subtyping identified ERBB2 amplification/overexpression as a high-risk feature strongly associated with poor survival. Patient-derived xenograft (PDX) models and a retrospective analysis of two clinical cases demonstrated that HER2-targeted antibody-drug conjugates (HER2-ADCs) significantly suppressed tumor growth and progression in OCCC patients with HER2 expression.</p><p><strong>Conclusions: </strong>In summary, our study establishes the comprehensive molecular atlas and a targeted therapeutic subtyping framework, revealing therapeutic vulnerabilities and providing novel insights for advancing precision oncology in OCCC management.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twelve years of genomic surveillance of vancomycin-resistant Enterococcus faecium: emergence of linear vanA and bacteriocin-carrying plasmids challenging infection control.","authors":"Ana C Almeida-Santos, Ana P Tedim, Bárbara Duarte, Ana P Pereira, Luís M Silva, Júlio Teixeira, Ana P Castro, Louise Roer, Anette M Hammerum, Henrik Hasman, Teresa M Coque, Carla Novais, Ana R Freitas, Luísa Peixe","doi":"10.1186/s13073-026-01656-4","DOIUrl":"10.1186/s13073-026-01656-4","url":null,"abstract":"<p><strong>Background: </strong>The epidemiology of vancomycin-resistant Enterococcus faecium (VREfm) varies across different countries, with a steady global increase. In Portugal, however, epidemiological data on clinical VREfm have been scarce since the early 2000s. This long-term study investigates VREfm isolates from human infections collected at a Porto hospital between 2010 and 2021.</p><p><strong>Methods: </strong>Two hundred VREfm isolates, mostly urinary (39%) were characterized by antimicrobial susceptibility testing to 8 antibiotics, chlorhexidine susceptibility, and PCR-based detection of vancomycin-resistance genes, virulence markers, plasmid replicases, and the bac43/T8 gene. Whole-genome sequencing, by Illumina, was used to assess clonal diversity (MLST, cgMLST, SNP phylogeny) and genomic content of antimicrobial resistance (AMR) genes, bacteriocins (76 genes) and putative virulence markers (35 genes). The plasmidome size and replicase initiation proteins of selected isolates was further improved by incorporating nanopore sequencing which enabled hybrid assemblies.</p><p><strong>Results: </strong>All isolates were multidrug resistant; 98% carried vanA, while two (1%) were resistant to linezolid (G2576T mutation). Chlorhexidine susceptibility remained stably low over time (MICs: 2-4 mg/L). The population was polyclonal, with a shift from ST18-like lineages to ST80 and ST117 dominance. While ARGs and virulence markers showed no clear association with clonal waves, bacteriocin profiles did, with bac43 becoming increasingly prevalent. ST117-CT24 emerged as the most persistent clone. The plasmidome comprised stable Rep3-like mobilizable plasmids carrying bacteriocins (bac43, bacAS5), RepA_N mega-plasmids harboring virulence/AMR/bacteriocins, and highly plastic medium-to-large vanA plasmids with diverse replicase initiation proteins. Strikingly, linear vanA plasmids (repUS78_pZY2) appeared in the most recent isolates, paralleling findings in vancomycin-variable E. faecium from the same hospital and VREfm from other countries.</p><p><strong>Conclusions: </strong>Our findings reveal dynamic clonal shifts, novel plasmid architectures, and the key role of bacteriocins in shaping clonal success in a WHO priority pathogen. Furthermore, we highlight the need for AMR surveillance frameworks to consider factors beyond conventional prevalence metrics and core-genome comparisons. Integrating intra-species genomic heterogeneity and non-traditional evolutionary indicators will be essential to more accurately predict, track, and ultimately mitigate the dissemination of multidrug-resistant human pathogens.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"18 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERG is a regulator of dynamic and reversible endothelial plasticity.","authors":"Kristen Schulz, Steven R Botts, Kai Ellis, Corey A Scipione, Nadiya Khyzha, Christy Ho, Rathnakumar Kumaragurubaran, Kyoko E Yuki, Joshua D Wythe, Clint L Miller, Michael D Wilson, Kathryn L Howe, Jason E Fish","doi":"10.1186/s13073-026-01638-6","DOIUrl":"10.1186/s13073-026-01638-6","url":null,"abstract":"<p><strong>Background: </strong>Endothelial cells (ECs) orchestrate vascular homeostasis and resilience but can undergo reprogramming into a mesenchymal-like phenotype through an endothelial-to-mesenchymal transition (EndMT). Crucially, EndMT is a linchpin underlying several cardiometabolic diseases, but is almost universally studied as an endpoint. The transcription factor ERG (ETS-related gene) is critical to the maintenance of EC identity and function, yet the dynamic transcriptional and functional consequences of ERG loss on EndMT programs, and whether this can be reversed, has not been explored.</p><p><strong>Methods: </strong>We modeled both acute and chronic ERG loss in human aortic ECs using siRNA knockdown and CRISPR/Cas9-mediated ERG deletion. We profiled temporal changes in chromatin accessibility (ATAC-seq), transcriptomic responses (RNA-seq), and endothelial phenotypes, including migration and barrier integrity. The temporal kinetics of ERG loss and restoration was assessed by comparing stable ERG knockout to transient ERG knockdown and recovery over time. The implications to human disease were deciphered by examining ERG gene regulatory networks in human atherosclerosis and linkage with genetic variation associated with human cardiovascular disease.</p><p><strong>Results: </strong>Analysis of gene regulatory networks revealed profound and dynamic rewiring of endothelial and mesenchymal transcriptional programs upon loss of ERG. While endothelial identity was rapidly lost by 24 h of ERG knockdown, acquisition of mesenchymal identity, barrier dysfunction, and enhanced cell migration required 72 h to manifest. Loss of ERG was accompanied by a rapid reduction in accessibility of ETS motifs and an extensive gain in open chromatin containing AP1 motifs. Disease-relevant endothelial dysfunction programs were associated with dynamically reorganized transcriptional networks. Importantly, restoration of ERG expression reversed EndMT gene regulatory networks and phenotypes.</p><p><strong>Conclusions: </strong>Overall, this study highlights the ETS factor, ERG, as an essential transcriptional safeguard of endothelial identity and function, and demonstrates that ERG loss initiates a progressive, yet reversible, EndMT program with EC identity loss preceding a gain of mesenchymal gene regulatory networks and phenotypes. This study establishes loss of ERG as an early initiating event in EndMT and suggests that ERG-targeted therapies may hold promise for promoting endothelial resilience.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"18 1","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative multi-omics profiling reveals distinct evolutionary and immunogenic features of brain oligometastasis in lung adenocarcinoma.","authors":"Rongxin Liao, Qian Yu, Yusheng Huang, Hengqiu He, Mengmeng Song, Xuan Gao, Lu Shen, Yihao Tao, Lin Li, Gang Xiao, Rui Kong, Cancan Wang, Shunping Huang, Xiaoyue Zhang, Zaicheng Xu, Rongrong Zhou, Zhenzhou Yang, Yuan Peng","doi":"10.1186/s13073-026-01664-4","DOIUrl":"https://doi.org/10.1186/s13073-026-01664-4","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence has demonstrated that lung cancer patients with brain oligometastases (oligo-BMs) could benefit from local radical therapies. Despite rapid advancements in the treatment of oligometastatic disease, the molecular determinants governing the oligometastatic phenotype in the central nervous system remain elusive.</p><p><strong>Methods: </strong>We performed 1021-panel sequencing, transcriptome profiling, DNA methylation mapping, and multiplex immunohistochemistry on 20 paired primary lung adenocarcinoma and oligo-BMs specimens to delineate their evolutionary dynamics and microenvironmental characteristics.</p><p><strong>Results: </strong>A pronounced intertumor heterogeneity was observed between primary tumors (PTs) and oligo-BMs, while intratumoral heterogeneity was conserved across lesions. Subclonal analysis and phylogenetic reconstruction demonstrated that oligo-BMs exhibited predominant polyclonal seeding patterns and parallel progression trajectories. Moreover, oligo-BMs displayed a more immunosuppressed microenvironment compared to PTs, characterized by attenuated immunogenic cell death signatures, downregulation of immune-activated pathways, and diminished infiltration of activated immune cells (including B cells, NK cells, and Th1 cells). The methylation levels at functional genomic regions were highly concordant between PTs and oligo-BMs. Notably, we identified NLGN1 as a potential regulator of oligo-BM, where the hypermethylation at its genebody regions was mechanistically associated with transcriptional upregulation. Clinical validation revealed that NLGN1 was specifically overexpressed in BMs compared to PTs and extracranial metastases, correlating with advanced pathological stages and poor prognosis. In vivo studies further confirmed NLGN1 promotes BM in mice.</p><p><strong>Conclusions: </strong>Our findings provide novel insights into the evolutionary trajectory, immune landscape and methylation pattern of oligo-BMs, potentially paving the way for the development of innovative therapeutic strategies for lung cancer patients with oligo-BMs.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional germline variants together with somatic mutations alter the integrity of cancer hallmark regulatory networks.","authors":"Jiawei Dai, Mate Posta, Michal Marczyk, Tao Qing, Balazs Gyorffy, Lajos Pusztai","doi":"10.1186/s13073-026-01644-8","DOIUrl":"10.1186/s13073-026-01644-8","url":null,"abstract":"","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of the COVID-19 pandemic and associated lifestyle changes on early-life microbiome development.","authors":"Evgenia Dikareva, Niels van Best, Liene Bervoets, Christina E West, Connor Rossel, Christel Driessen, Monique Mommers, John Penders","doi":"10.1186/s13073-026-01660-8","DOIUrl":"https://doi.org/10.1186/s13073-026-01660-8","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic triggered rapid, population-wide behavioral and environmental changes, offering a unique natural experiment to study how early-life microbiome development responds to abrupt shifts in social and hygiene-related exposures.</p><p><strong>Methods: </strong>Using longitudinal data from 139 infants in the Dutch LucKi Gut study, we compared gut microbiome development in fecal samples collected before and during the pandemic. Whole metagenome sequencing of 808 stool samples was performed across nine time points in the first 14 months of life. An exposure index (EI) capturing variation in household-level pandemic-related behaviors was constructed for the 36 infants with samples collected during the COVID-pandemic to quantify variations in social distancing, lifestyle and hygiene measures.</p><p><strong>Results: </strong>Microbial richness and diversity increased with age, following established developmental trajectories. However, from 6 months onward, the COVID-19 pandemic independently shaped gut microbial composition, explaining up to 2.7% of variation by 11 months of age (Q-value = 0.006). Forty-four species were differentially abundant in pandemic-era samples, including depletion of Gordonibacter pamelaeae and several Actinomyces species. Notably, greater environmental exposure (higher EI scores) was associated with lower abundance of G. pamelaeae, a microbe implicated in bile acid and immunomodulatory metabolism.</p><p><strong>Conclusions: </strong>This is the first longitudinal whole-genome sequencing study to demonstrate that pandemic-related behavioral changes measurably altered infant gut microbiota maturation. These findings highlight the sensitivity of microbiome development to societal-level environmental disruptions and suggest that early-life microbial exposures, modulated by hygiene and social behavior, may carry long-term implications for child health.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single base focal hypermutation cooccurs with structural variation as an early event in advanced prostate tumourigenesis with ancestry specific independence: a multi-ancestral observational study.","authors":"Jue Jiang, Avraam Tapinos, Ruotian Huang, M S Riana Bornman, Phillip D Stricker, Shingai B A Mutambirwa, David C Wedge, Weerachai Jaratlerdsiri, Vanessa M Hayes","doi":"10.1186/s13073-026-01647-5","DOIUrl":"https://doi.org/10.1186/s13073-026-01647-5","url":null,"abstract":"","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}