Pub Date : 2025-12-05DOI: 10.1038/s41587-025-02954-9
Lisa Melton
This year’s most popular stories are a testament to biotech ingenuity and a cause for celebration: the gene editing triumph that cured ‘baby KJ’ of a rare genetic disorder in record time; the bispecific molecules that trick HIV out of cells to destroy them; how Brazil is producing its own affordable CAR T cells; and the shift in regulators’ demands for animal testing for certain drug classes.
{"title":"Top ten news stories in 2025","authors":"Lisa Melton","doi":"10.1038/s41587-025-02954-9","DOIUrl":"10.1038/s41587-025-02954-9","url":null,"abstract":"This year’s most popular stories are a testament to biotech ingenuity and a cause for celebration: the gene editing triumph that cured ‘baby KJ’ of a rare genetic disorder in record time; the bispecific molecules that trick HIV out of cells to destroy them; how Brazil is producing its own affordable CAR T cells; and the shift in regulators’ demands for animal testing for certain drug classes.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 12","pages":"1891-1892"},"PeriodicalIF":41.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680726","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 : 2025-12-05DOI: 10.1038/s41587-025-02961-w
Nature Biotechnology editors pick their favorite research articles from 2025.
《自然生物技术》的编辑们从2025年挑选了他们最喜欢的研究文章。
{"title":"2025: research in review","authors":"","doi":"10.1038/s41587-025-02961-w","DOIUrl":"10.1038/s41587-025-02961-w","url":null,"abstract":"Nature Biotechnology editors pick their favorite research articles from 2025.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 12","pages":"1889-1890"},"PeriodicalIF":41.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41587-025-02961-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680196","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}
Pub Date : 2025-12-03DOI: 10.1038/s41587-025-02914-3
Elliott G Swanson,Yizi Mao,Benjamin J Mallory,Mitchell R Vollger,Stephanie C Bohaczuk,Christopher B Oliveira,Daniel B Lyon,Jane Ranchalis,Nancy L Parmalee,Barak A Cohen,James T Bennett,Andrew B Stergachis
Gene regulation is orchestrated by the co-binding of proteins along chromosome-length chromatin fibers within single cells, yet the heterogeneity of this occupancy between haplotypes and cells remains poorly resolved in diploid organisms. Here we present Deaminase-Assisted single-molecule chromatin Fiber sequencing (DAF-seq), which enables single-molecule footprinting at near-nucleotide resolution while synchronously profiling single-molecule chromatin states and DNA sequence. DAF-seq illuminates cooperative protein occupancy at individual regulatory elements and resolves the functional impact of somatic variants and rare chromatin epialleles. Single-cell DAF-seq (scDAF-seq) generates chromosome-length protein co-occupancy maps across 99% of each individual cell's mappable genome. scDAF-seq uncovers extensive chromatin plasticity both within and between single diploid cells, with chromatin actuation diverging by 61% between haplotypes within a cell, and 63% between cells. Moreover, we find that regulatory elements are preferentially co-actuated along the same fiber in a distance-dependent manner that mirrors cohesin-mediated loops. Overall, DAF-seq enables the characterization of protein occupancy across entire chromosomes with single-nucleotide, single-molecule, single-haplotype and single-cell precision.
{"title":"Mapping single-cell diploid chromatin fiber architectures using DAF-seq.","authors":"Elliott G Swanson,Yizi Mao,Benjamin J Mallory,Mitchell R Vollger,Stephanie C Bohaczuk,Christopher B Oliveira,Daniel B Lyon,Jane Ranchalis,Nancy L Parmalee,Barak A Cohen,James T Bennett,Andrew B Stergachis","doi":"10.1038/s41587-025-02914-3","DOIUrl":"https://doi.org/10.1038/s41587-025-02914-3","url":null,"abstract":"Gene regulation is orchestrated by the co-binding of proteins along chromosome-length chromatin fibers within single cells, yet the heterogeneity of this occupancy between haplotypes and cells remains poorly resolved in diploid organisms. Here we present Deaminase-Assisted single-molecule chromatin Fiber sequencing (DAF-seq), which enables single-molecule footprinting at near-nucleotide resolution while synchronously profiling single-molecule chromatin states and DNA sequence. DAF-seq illuminates cooperative protein occupancy at individual regulatory elements and resolves the functional impact of somatic variants and rare chromatin epialleles. Single-cell DAF-seq (scDAF-seq) generates chromosome-length protein co-occupancy maps across 99% of each individual cell's mappable genome. scDAF-seq uncovers extensive chromatin plasticity both within and between single diploid cells, with chromatin actuation diverging by 61% between haplotypes within a cell, and 63% between cells. Moreover, we find that regulatory elements are preferentially co-actuated along the same fiber in a distance-dependent manner that mirrors cohesin-mediated loops. Overall, DAF-seq enables the characterization of protein occupancy across entire chromosomes with single-nucleotide, single-molecule, single-haplotype and single-cell precision.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"22 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145663917","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 : 2025-12-03DOI: 10.1038/s41587-025-02811-9
Jasmine T Plummer,Felipe Segato Dezem,David P Cook,Jiwoon Park,Luke Zhang,Yutian Liu,Maycon Marção,Hannah DuBose,Arjumand Wani,Kellie Wise,Michael Roach,Kate Harvey,Taopeng Wang,Kirk B Jensen,Natalia Morosini,Roberto De Gregorio,Alicia Alonso,Shauna Lee Houlihan,Robert E Schwartz,Erika Hissong,Catherine Snopkowski,Jeffrey L Wrana,Natalie Ryan,Lisa M Butler,George Church,Alexander Swarbrick,Christopher E Mason,Luciano G Martelotto
Spatial transcriptomics lacks standardized metrics for evaluating imaging-based in situ hybridization technologies across sites. In this study, we generated the Spatial Touchstone (ST) dataset from six tissue types across several global sites with centralized sectioning, analyzed on both Xenium and CosMx platforms. These platforms were selected for their widespread use and distinct chemistries. We assessed reproducibility, sensitivity, dynamic ranges, signal-to-noise ratio, false discovery rates, cell type annotation and congruence with single-cell profiling. This study offers ST standardized operating procedures (STSOPs) and an open-source software, SpatialQM, enabling evaluation of samples across all technical metrics and direct imputation of cell annotations. The generated imaging-based spatial transcriptomics data repository comprises 254 spatial profiles, incorporating both public and newly generated ST datasets in a web-based application, which enables analysis and comparison of user data against an extensive collection of imaging-based datasets. Finally, we establish best practices and metrics to evaluate and integrate imaging-based multi-omics data from single cells into spatial transcriptomics to spatial proteomics.
{"title":"Standardized metrics for assessment and reproducibility of imaging-based spatial transcriptomics datasets.","authors":"Jasmine T Plummer,Felipe Segato Dezem,David P Cook,Jiwoon Park,Luke Zhang,Yutian Liu,Maycon Marção,Hannah DuBose,Arjumand Wani,Kellie Wise,Michael Roach,Kate Harvey,Taopeng Wang,Kirk B Jensen,Natalia Morosini,Roberto De Gregorio,Alicia Alonso,Shauna Lee Houlihan,Robert E Schwartz,Erika Hissong,Catherine Snopkowski,Jeffrey L Wrana,Natalie Ryan,Lisa M Butler,George Church,Alexander Swarbrick,Christopher E Mason,Luciano G Martelotto","doi":"10.1038/s41587-025-02811-9","DOIUrl":"https://doi.org/10.1038/s41587-025-02811-9","url":null,"abstract":"Spatial transcriptomics lacks standardized metrics for evaluating imaging-based in situ hybridization technologies across sites. In this study, we generated the Spatial Touchstone (ST) dataset from six tissue types across several global sites with centralized sectioning, analyzed on both Xenium and CosMx platforms. These platforms were selected for their widespread use and distinct chemistries. We assessed reproducibility, sensitivity, dynamic ranges, signal-to-noise ratio, false discovery rates, cell type annotation and congruence with single-cell profiling. This study offers ST standardized operating procedures (STSOPs) and an open-source software, SpatialQM, enabling evaluation of samples across all technical metrics and direct imputation of cell annotations. The generated imaging-based spatial transcriptomics data repository comprises 254 spatial profiles, incorporating both public and newly generated ST datasets in a web-based application, which enables analysis and comparison of user data against an extensive collection of imaging-based datasets. Finally, we establish best practices and metrics to evaluate and integrate imaging-based multi-omics data from single cells into spatial transcriptomics to spatial proteomics.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"41 3 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664140","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 : 2025-12-02DOI: 10.1038/s41587-025-02936-x
Kasey S Love,Kate E Galloway
{"title":"Modulating RNA condensates to control cell fate.","authors":"Kasey S Love,Kate E Galloway","doi":"10.1038/s41587-025-02936-x","DOIUrl":"https://doi.org/10.1038/s41587-025-02936-x","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"198200 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656854","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 : 2025-12-02DOI: 10.1038/s41587-025-02934-z
Joseph P. Allen
{"title":"March-in rights under the Bayh–Dole Act undermine the US drug development sector without lowering drug costs","authors":"Joseph P. Allen","doi":"10.1038/s41587-025-02934-z","DOIUrl":"10.1038/s41587-025-02934-z","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 12","pages":"1909-1909"},"PeriodicalIF":41.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656853","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 : 2025-12-02DOI: 10.1038/s41587-025-02943-y
Sarah M. E. Gabriele, Matthew J. Martin, Aaron S. Kesselheim, S. Sean Tu
{"title":"Gabriele et al. reply","authors":"Sarah M. E. Gabriele, Matthew J. Martin, Aaron S. Kesselheim, S. Sean Tu","doi":"10.1038/s41587-025-02943-y","DOIUrl":"10.1038/s41587-025-02943-y","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 12","pages":"1910-1910"},"PeriodicalIF":41.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661484","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 : 2025-11-26DOI: 10.1038/s41587-025-02904-5
Sevahn K. Vorperian, Lucas M. Dennis, Anna Hupalowska, Jennifer E. Rood, Stephen R. Quake
Cell-free nucleic acid (cfNA) liquid biopsy offers a versatile, noninvasive alternative to needle biopsy procedures for the diagnosis or surveillance of a broad range of diseases and physiological conditions. Although these noninvasive molecular measurements enable diagnostic biomarker discovery, they often lack the cellular resolution afforded by invasive needle biopsy. Cell type-specific changes frequently form the basis of disease and contribute to the molecular changes observed in a cfNA liquid biopsy. Recent experimental and computational advances in cfNA detection, alongside detailed molecular definitions across cell types of the human body from single-cell transcriptomic data, can enable cell type inference. In this Review, we delineate the respective strengths of cell-free DNA and cell-free RNA relative to the diagnostic use case. We then describe computational frameworks to infer cell type contributions in cfNA and the distinct opportunity afforded by single-cell transcriptomic data. Finally, we highlight current applications, future directions, and outstanding questions related to this paradigm in cfNA liquid biopsy. Recent computational and experimental advances enable noninvasive inference of cell type in cell-free nucleic acid liquid biopsies, expanding their use across diverse settings.
{"title":"Cell type inference in cell-free nucleic acid liquid biopsy","authors":"Sevahn K. Vorperian, Lucas M. Dennis, Anna Hupalowska, Jennifer E. Rood, Stephen R. Quake","doi":"10.1038/s41587-025-02904-5","DOIUrl":"10.1038/s41587-025-02904-5","url":null,"abstract":"Cell-free nucleic acid (cfNA) liquid biopsy offers a versatile, noninvasive alternative to needle biopsy procedures for the diagnosis or surveillance of a broad range of diseases and physiological conditions. Although these noninvasive molecular measurements enable diagnostic biomarker discovery, they often lack the cellular resolution afforded by invasive needle biopsy. Cell type-specific changes frequently form the basis of disease and contribute to the molecular changes observed in a cfNA liquid biopsy. Recent experimental and computational advances in cfNA detection, alongside detailed molecular definitions across cell types of the human body from single-cell transcriptomic data, can enable cell type inference. In this Review, we delineate the respective strengths of cell-free DNA and cell-free RNA relative to the diagnostic use case. We then describe computational frameworks to infer cell type contributions in cfNA and the distinct opportunity afforded by single-cell transcriptomic data. Finally, we highlight current applications, future directions, and outstanding questions related to this paradigm in cfNA liquid biopsy. Recent computational and experimental advances enable noninvasive inference of cell type in cell-free nucleic acid liquid biopsies, expanding their use across diverse settings.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 12","pages":"1940-1953"},"PeriodicalIF":41.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599676","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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