Pub Date : 2025-11-03DOI: 10.1038/s41576-025-00909-z
Kathryn E. Holt
The scale-up of microbial genomics has seen notable advances in understanding the dynamics of antimicrobial resistance (AMR) across species, environments and ecosystems. To gain meaningful insights that can ultimately inform AMR control strategies, stronger analytical frameworks are needed that integrate data across temporal, spatial and molecular scales. Microbial genomics can improve our understanding of antimicrobial resistance dynamics across ecosystems. In this Comment, Kathryn Holt emphasizes the interconnectedness of human, animal and environmental health and calls for greater integration of microbial genomic data through robust analytical frameworks to unravel the complexity of antimicrobial resistance dynamics.
{"title":"Microbial genomics for antimicrobial resistance ecology and action","authors":"Kathryn E. Holt","doi":"10.1038/s41576-025-00909-z","DOIUrl":"10.1038/s41576-025-00909-z","url":null,"abstract":"The scale-up of microbial genomics has seen notable advances in understanding the dynamics of antimicrobial resistance (AMR) across species, environments and ecosystems. To gain meaningful insights that can ultimately inform AMR control strategies, stronger analytical frameworks are needed that integrate data across temporal, spatial and molecular scales. Microbial genomics can improve our understanding of antimicrobial resistance dynamics across ecosystems. In this Comment, Kathryn Holt emphasizes the interconnectedness of human, animal and environmental health and calls for greater integration of microbial genomic data through robust analytical frameworks to unravel the complexity of antimicrobial resistance dynamics.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 1","pages":"7-8"},"PeriodicalIF":52.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427382","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}
Pub Date : 2025-11-03DOI: 10.1038/s41576-025-00914-2
Peter K. Koo
In this Journal Club, Peter Koo reflects on the 2021 publication of Enformer and its impact on the use of deep learning for modelling the regulatory genome.
{"title":"Decoding the regulatory genome with large-scale deep learning","authors":"Peter K. Koo","doi":"10.1038/s41576-025-00914-2","DOIUrl":"10.1038/s41576-025-00914-2","url":null,"abstract":"In this Journal Club, Peter Koo reflects on the 2021 publication of Enformer and its impact on the use of deep learning for modelling the regulatory genome.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 2","pages":"117-117"},"PeriodicalIF":52.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427381","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}
Pub Date : 2025-10-30DOI: 10.1038/s41576-025-00910-6
Jaime Martinez-Urtaza
Jaime Martinez-Urtaza reflects on two papers by Smith et al., who found that bacteria exist along a continuum from clonal to recombining populations, and introduced the concept of an ‘epidemic’ microbial population structure.
{"title":"From clonality to complexity: a journey through microbial ecology and evolution","authors":"Jaime Martinez-Urtaza","doi":"10.1038/s41576-025-00910-6","DOIUrl":"10.1038/s41576-025-00910-6","url":null,"abstract":"Jaime Martinez-Urtaza reflects on two papers by Smith et al., who found that bacteria exist along a continuum from clonal to recombining populations, and introduced the concept of an ‘epidemic’ microbial population structure.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 1","pages":"10-10"},"PeriodicalIF":52.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145397426","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}
Pub Date : 2025-10-30DOI: 10.1038/s41576-025-00911-5
Luis H. Orellana
In this Journal Club, Luis Orellana recalls a 2005 publication by Konstantinidis and Tiedje that introduced average nucleotide identity as a sequence-based metric to determine the relatedness between two genomes, which helped to operationally define bacterial species.
{"title":"Average nucleotide identity — the backbone of modern ecological genomics","authors":"Luis H. Orellana","doi":"10.1038/s41576-025-00911-5","DOIUrl":"10.1038/s41576-025-00911-5","url":null,"abstract":"In this Journal Club, Luis Orellana recalls a 2005 publication by Konstantinidis and Tiedje that introduced average nucleotide identity as a sequence-based metric to determine the relatedness between two genomes, which helped to operationally define bacterial species.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 1","pages":"9-9"},"PeriodicalIF":52.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145397424","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}
Pub Date : 2025-10-22DOI: 10.1038/s41576-025-00905-3
Jean Fan
Jean Fan recounts a 2015 paper by Martincorena et al. that revealed oncogenic mutations in normal tissues, also highlighting how the latest spatial technologies can now be used to study the spatial contextual impact of these mutations.
Jean Fan讲述了Martincorena等人在2015年发表的一篇论文，该论文揭示了正常组织中的致癌突变，并强调了现在如何使用最新的空间技术来研究这些突变的空间背景影响。
{"title":"Revisiting the somatic mutation theory of cancer pathogenesis","authors":"Jean Fan","doi":"10.1038/s41576-025-00905-3","DOIUrl":"10.1038/s41576-025-00905-3","url":null,"abstract":"Jean Fan recounts a 2015 paper by Martincorena et al. that revealed oncogenic mutations in normal tissues, also highlighting how the latest spatial technologies can now be used to study the spatial contextual impact of these mutations.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 2","pages":"116-116"},"PeriodicalIF":52.0,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339430","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}
Pub Date : 2025-10-17DOI: 10.1038/s41576-025-00899-y
Samantha A Morris
Manipulating cell identity through transcription factor-mediated reprogramming, induced pluripotency or directed differentiation holds promise for disease modelling and regenerative medicine. Yet the cells produced by these methods often do not fully recapitulate the molecular and functional characteristics of their native counterparts. Immaturity, low fidelity and heterogeneity remain barriers, limiting reliability for modelling human disease and therapeutic use. Recent advances in single-cell genomic technologies, integrative computational frameworks and emerging molecular recording tools are beginning to reveal the mechanisms underlying incomplete or inefficient reprogramming and highlight tractable failure points. Together, these approaches could support mechanism-guided protocol design and stepwise gains in fidelity, maturity and purity, potentially moving engineered cells towards clinical relevance and informing design principles for next-generation reprogramming strategies.
{"title":"Redefining cellular reprogramming with advanced genomic technologies.","authors":"Samantha A Morris","doi":"10.1038/s41576-025-00899-y","DOIUrl":"https://doi.org/10.1038/s41576-025-00899-y","url":null,"abstract":"Manipulating cell identity through transcription factor-mediated reprogramming, induced pluripotency or directed differentiation holds promise for disease modelling and regenerative medicine. Yet the cells produced by these methods often do not fully recapitulate the molecular and functional characteristics of their native counterparts. Immaturity, low fidelity and heterogeneity remain barriers, limiting reliability for modelling human disease and therapeutic use. Recent advances in single-cell genomic technologies, integrative computational frameworks and emerging molecular recording tools are beginning to reveal the mechanisms underlying incomplete or inefficient reprogramming and highlight tractable failure points. Together, these approaches could support mechanism-guided protocol design and stepwise gains in fidelity, maturity and purity, potentially moving engineered cells towards clinical relevance and informing design principles for next-generation reprogramming strategies.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"29 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311243","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}
Pub Date : 2025-10-16DOI: 10.1038/s41576-025-00906-2
Nicole S. Webster
Microorganisms are central to climate stability, food security and biodiversity, yet they remain absent from global sustainability frameworks. Recognizing and mobilizing their power is essential if we are to meet the challenges of the coming decades. Microorganisms are central to climate stability, food security and biodiversity, yet they remain absent from global sustainability frameworks. In this Comment, Nicole Webster highlights the power of eco-evolutionary genomics in transforming sustainability science and calls for the inclusion of microbes in global policies.
{"title":"Microorganisms as architects of a sustainable future","authors":"Nicole S. Webster","doi":"10.1038/s41576-025-00906-2","DOIUrl":"10.1038/s41576-025-00906-2","url":null,"abstract":"Microorganisms are central to climate stability, food security and biodiversity, yet they remain absent from global sustainability frameworks. Recognizing and mobilizing their power is essential if we are to meet the challenges of the coming decades. Microorganisms are central to climate stability, food security and biodiversity, yet they remain absent from global sustainability frameworks. In this Comment, Nicole Webster highlights the power of eco-evolutionary genomics in transforming sustainability science and calls for the inclusion of microbes in global policies.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 1","pages":"5-6"},"PeriodicalIF":52.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305593","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}
Pub Date : 2025-10-10DOI: 10.1038/s41576-025-00900-8
Iftikhar J Kullo
Genome-wide association studies have identified thousands of single-nucleotide variants that are associated with complex traits, including cardiometabolic diseases, cancers and neurological disorders. Polygenic risk scores (PRSs), which aggregate the effects of these variants, can help to identify individuals who are at increased risk of developing such diseases. As PRSs are typically only weakly associated with conventional risk factors for these diseases, they have incremental predictive value and are beginning to be incorporated into clinical practice to guide early detection and preventive strategies. However, challenges to their use - such as suboptimal precision, poor transferability across diverse populations and low familiarity among patients and providers with the concept of polygenic risk - must be addressed before their broader clinical adoption. This Review explores the current state of the field, highlights key challenges and outlines future directions for the use of PRSs to improve risk prediction and to advance personalized prevention in clinical care.
{"title":"Clinical use of polygenic risk scores: current status, barriers and future directions.","authors":"Iftikhar J Kullo","doi":"10.1038/s41576-025-00900-8","DOIUrl":"https://doi.org/10.1038/s41576-025-00900-8","url":null,"abstract":"Genome-wide association studies have identified thousands of single-nucleotide variants that are associated with complex traits, including cardiometabolic diseases, cancers and neurological disorders. Polygenic risk scores (PRSs), which aggregate the effects of these variants, can help to identify individuals who are at increased risk of developing such diseases. As PRSs are typically only weakly associated with conventional risk factors for these diseases, they have incremental predictive value and are beginning to be incorporated into clinical practice to guide early detection and preventive strategies. However, challenges to their use - such as suboptimal precision, poor transferability across diverse populations and low familiarity among patients and providers with the concept of polygenic risk - must be addressed before their broader clinical adoption. This Review explores the current state of the field, highlights key challenges and outlines future directions for the use of PRSs to improve risk prediction and to advance personalized prevention in clinical care.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"120 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261296","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}
Pub Date : 2025-10-08DOI: 10.1038/s41576-025-00896-1
Manfred Kayser
Recent advances in forensic genetics, driven by technological innovation coupled with the use of an expanding range of nucleic acid markers, have markedly improved the scope, accuracy and reliability of evidential information obtainable from human biological traces recovered at crime scenes. The majority of these biomarkers have been identified using non-targeted omics approaches, including genomics, transcriptomics, epigenomics and microbiome profiling. Moreover, targeted massively parallel sequencing, in some cases non-targeted whole-genome sequencing, are being applied to the analyses of biological trace material. These approaches and methods are being used for the identification of perpetrators (including monozygotic twins), their relatives or victims of criminal activities; the prediction of phenotypic and behavioural traits of unknown individuals; and the determination of trace characteristics, including tissue type and time of deposition. Recent advances in forensic genetics have improved the range, precision and reliability of forensic information obtainable from biological trace material. The author reviews how non-targeted and targeted omics approaches and methods are improving crime scene analyses being applied for the identification of perpetrators and their relatives or victims, the prediction of phenotypic traits, and the determination of trace characteristics.
{"title":"Forensic genetics in the omics era","authors":"Manfred Kayser","doi":"10.1038/s41576-025-00896-1","DOIUrl":"10.1038/s41576-025-00896-1","url":null,"abstract":"Recent advances in forensic genetics, driven by technological innovation coupled with the use of an expanding range of nucleic acid markers, have markedly improved the scope, accuracy and reliability of evidential information obtainable from human biological traces recovered at crime scenes. The majority of these biomarkers have been identified using non-targeted omics approaches, including genomics, transcriptomics, epigenomics and microbiome profiling. Moreover, targeted massively parallel sequencing, in some cases non-targeted whole-genome sequencing, are being applied to the analyses of biological trace material. These approaches and methods are being used for the identification of perpetrators (including monozygotic twins), their relatives or victims of criminal activities; the prediction of phenotypic and behavioural traits of unknown individuals; and the determination of trace characteristics, including tissue type and time of deposition. Recent advances in forensic genetics have improved the range, precision and reliability of forensic information obtainable from biological trace material. The author reviews how non-targeted and targeted omics approaches and methods are improving crime scene analyses being applied for the identification of perpetrators and their relatives or victims, the prediction of phenotypic traits, and the determination of trace characteristics.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 2","pages":"170-186"},"PeriodicalIF":52.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246592","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}
Pub Date : 2025-10-07DOI: 10.1038/s41576-025-00902-6
Tzachi Hagai
In this Journal Club, Tzachi Hagai highlights a 2005 paper by Sawyer et al. that tested the functional relationship of evolutionary changes in immune genes with infection outcomes.
{"title":"Host–pathogen interactions shape human evolution and future pandemics","authors":"Tzachi Hagai","doi":"10.1038/s41576-025-00902-6","DOIUrl":"10.1038/s41576-025-00902-6","url":null,"abstract":"In this Journal Club, Tzachi Hagai highlights a 2005 paper by Sawyer et al. that tested the functional relationship of evolutionary changes in immune genes with infection outcomes.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 2","pages":"115-115"},"PeriodicalIF":52.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241094","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}
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