Nature MethodsPub Date : 2026-08-11DOI: 10.1038/s41592-026-03199-3
Xiaolei Yu, Vincent Mukwaya, Minxing Yue, Shuo Yang, Qian Li, Weili Zhao, Chunhai Fan, Lin Wang, Yingxi Zhao, Hongkai Yang, Jiacan Su, Li Wang, Hongjing Dou
{"title":"Decoding mechanoregulation in immunological synapses using biomimetic artificial cells","authors":"Xiaolei Yu, Vincent Mukwaya, Minxing Yue, Shuo Yang, Qian Li, Weili Zhao, Chunhai Fan, Lin Wang, Yingxi Zhao, Hongkai Yang, Jiacan Su, Li Wang, Hongjing Dou","doi":"10.1038/s41592-026-03199-3","DOIUrl":"10.1038/s41592-026-03199-3","url":null,"abstract":"Mechanical force-driven signaling has emerged as a key regulator of cell–cell interactions (CCIs), which can enhance immune cell function. However, current biochemical approaches for studying CCIs offer minimal direct control over cellular bulk phenotypes, while synthetic biomaterial systems fail to mimic the dynamic complexity of cells. Here we introduce kpiCells, a biomaterial-based platform that uses a biomimetic membrane–endoplasmic architecture to enable finely tuned phenocopying of cellular states via modular mechanical, chemical and topographical inputs. We demonstrate that kpiCells can engage in physiological CCIs and reproduce critical subcellular features. In T cell systems, kpiCells enable integrated interrogation of afferent mechanosensing pathways and efferent force-exertion pathways, and support measurement of piconewton-scale forces at individual T cell antigen receptors as well as single cell–cell force fingerprints that define activation thresholds. This work establishes kpiCells as a bionic model that enables synthetic material design with the level of functional complexity approaching living cell systems. kpiCells are a biomimetic artificial cell system to investigate mechanoregulation in cell–cell interactions.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 9","pages":"1882-1894"},"PeriodicalIF":28.3,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713303","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}
Nature MethodsPub Date : 2026-08-06DOI: 10.1038/s41592-026-03189-5
Nina Vogt
{"title":"Neuronal recordings with DNA origami","authors":"Nina Vogt","doi":"10.1038/s41592-026-03189-5","DOIUrl":"10.1038/s41592-026-03189-5","url":null,"abstract":"","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 8","pages":"1486-1486"},"PeriodicalIF":28.3,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685293","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}
Nature MethodsPub Date : 2026-08-06DOI: 10.1038/s41592-026-03197-5
{"title":"Early-career researcher co-review, one year in","authors":"","doi":"10.1038/s41592-026-03197-5","DOIUrl":"10.1038/s41592-026-03197-5","url":null,"abstract":"A little more than one year ago, Nature Methods rolled out a program to formally recognize early-career researcher contributions to our peer review process. Here we provide an update on the program’s success.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 8","pages":"1471-1471"},"PeriodicalIF":28.3,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41592-026-03197-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685330","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}
Nature MethodsPub Date : 2026-08-05DOI: 10.1038/s41592-026-03177-9
Arttu Jolma, Aldo Hernandez-Corchado, Ally W. H. Yang, Ali Fathi, Kaitlin U. Laverty, Alexander Brechalov, Rozita Razavi, Mihai Albu, Hong Zheng, The Codebook Consortium, Ivan V. Kulakovskiy, Hamed S. Najafabadi, Timothy R. Hughes
{"title":"GHT-SELEX demonstrates unexpectedly high intrinsic sequence specificity and complex DNA binding of many human transcription factors","authors":"Arttu Jolma, Aldo Hernandez-Corchado, Ally W. H. Yang, Ali Fathi, Kaitlin U. Laverty, Alexander Brechalov, Rozita Razavi, Mihai Albu, Hong Zheng, The Codebook Consortium, Ivan V. Kulakovskiy, Hamed S. Najafabadi, Timothy R. Hughes","doi":"10.1038/s41592-026-03177-9","DOIUrl":"10.1038/s41592-026-03177-9","url":null,"abstract":"There is ongoing debate regarding the degree to which transcription factors (TFs) independently specify genomic binding: TF binding motifs are typically short and degenerate, yielding many more binding site predictions than observed in cells. Here we present genomic high-throughput SELEX (GHT-SELEX)—a scalable method that surveys intrinsic binding of purified TFs to the fragmented, naked and unmodified genome. GHT-SELEX peaks for 179 diverse human TFs display surprisingly high overlap with chromatin immunoprecipitation sequencing peaks for the same TF. Comparable overlap can be obtained from motifs using appropriate analytical approaches. For C2H2 zinc finger (zf) proteins—the largest class of human TFs—GHT-SELEX shows that modular, alternative engagement of C2H2-zf domains is the norm, enabling several types of distinct target sites, and frequently involving internal duplication and divergence within the C2H2-zf array. Altogether, it is common for TFs to delineate a large fraction of in vivo genomic binding sites independently of other cellular factors. GHT-SELEX—high-throughput SELEX with fragmented genomic DNA—shows that transcription factors can be rather particular about which genomic loci they bind, and that C2H2 zinc finger proteins often engage different fingers at different sites.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 9","pages":"1775-1785"},"PeriodicalIF":28.3,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679411","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}
Nature MethodsPub Date : 2026-07-31DOI: 10.1038/s41592-026-03140-8
Andrew Causer, Tianyao Lu, Jurgen Kriel, Joel J. D. Moffet, Christopher C. J. Fitzgerald, Andrew Newman, Hani Vu, Xiao Tan, Tuan Vo, Cedric Cui, Vinod K. Narayana, James R. Whittle, Sarah A. Best, Saskia Freytag, Quan Nguyen
{"title":"SpaMTP: integrative statistical analysis and visualization of spatial metabolomics and transcriptomics data","authors":"Andrew Causer, Tianyao Lu, Jurgen Kriel, Joel J. D. Moffet, Christopher C. J. Fitzgerald, Andrew Newman, Hani Vu, Xiao Tan, Tuan Vo, Cedric Cui, Vinod K. Narayana, James R. Whittle, Sarah A. Best, Saskia Freytag, Quan Nguyen","doi":"10.1038/s41592-026-03140-8","DOIUrl":"10.1038/s41592-026-03140-8","url":null,"abstract":"Spatially resolved multimodal data enable the exploration of transcriptional, proteomic and metabolic regulation, yet analytical tools to integrate these spatial omics modalities, particularly spatial metabolomics, remain limited. We developed SpaMTP, an end-to-end framework that implements functions within a common Seurat architecture. It introduces analyses for metabolite annotation, joint clustering, enrichment tests, spatial alignment, multimodal integration, visualization and seamless software interoperability. Its utility is demonstrated across different biological systems. SpaMTP enables comprehensive joint analysis of spatial metabolomics and transcriptomics data.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 8","pages":"1501-1506"},"PeriodicalIF":28.3,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648553","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}
Nature MethodsPub Date : 2026-07-31DOI: 10.1038/s41592-026-03162-2
Yuval Bussi, Dana Shainshein, Eli Ovits, Sarah Posner, Nofar Azulay, Noa Maimon, Tal Keidar Haran, Raz Ben-Uri, Caitlin Brown, Noam Schuldiner, Eylon Yaniv, David Van Valen, Idan Milo, Ofer Elhanani, Robert Schiemann, Leeat Keren
{"title":"CellTune: an integrative software for accurate cell classification in spatial proteomics","authors":"Yuval Bussi, Dana Shainshein, Eli Ovits, Sarah Posner, Nofar Azulay, Noa Maimon, Tal Keidar Haran, Raz Ben-Uri, Caitlin Brown, Noam Schuldiner, Eylon Yaniv, David Van Valen, Idan Milo, Ofer Elhanani, Robert Schiemann, Leeat Keren","doi":"10.1038/s41592-026-03162-2","DOIUrl":"10.1038/s41592-026-03162-2","url":null,"abstract":"Spatial proteomics measures multiple proteins in situ, capturing tissue complexity. However, cell classification in densely packed tissues remains challenging because of the lack of efficient classification algorithms, annotation tools and high-quality labeled datasets to benchmark computational methods. We introduce CellTune, an integrated software for analysis of large spatial proteomics datasets, which streamlines precise cell classification through an optimized human-in-the-loop active learning workflow. It advances core capabilities for analysis of large datasets with an intuitive and code-free interface. To evaluate CellTune, we created CellTuneDepot, a resource of 40,000 manually annotated cells and 3.5 million high-quality labeled cells across 60 cell types. CellTune outperforms alternative methods, achieving accuracy comparable to human performance while enabling increased classification resolution and discovery of novel cell types. Together, CellTune and CellTuneDepot provide researchers with a tool for state-of-the-art classification accuracy and resolution at scale to drive biological insights. CellTune enables high precision analysis of spatial proteomics datasets through a human-in-the-loop active learning workflow.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 8","pages":"1574-1587"},"PeriodicalIF":28.3,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648638","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}