Nature MethodsPub Date : 2026-10-13DOI: 10.1038/s41592-026-03255-y
Olena S Oliinyk, Yirui Xu, Jinhuan Luo, Kateryna O Tokarchuk, Kyrylo Yu Manoilov, Josie van de Klashorst, Matthew P Eyring, Mu-En Wang, Ming Chen, Pengfei Song, John W Hickey, Junjie Yao, Vladislav V Verkhusha
{"title":"Near-infrared photochromic miniprotein enables photoacoustic molecular imaging of acute inflammation and intracellular antigens.","authors":"Olena S Oliinyk, Yirui Xu, Jinhuan Luo, Kateryna O Tokarchuk, Kyrylo Yu Manoilov, Josie van de Klashorst, Matthew P Eyring, Mu-En Wang, Ming Chen, Pengfei Song, John W Hickey, Junjie Yao, Vladislav V Verkhusha","doi":"10.1038/s41592-026-03255-y","DOIUrl":"https://doi.org/10.1038/s41592-026-03255-y","url":null,"abstract":"<p><p>Using near-infrared photoswitchable photochromic genetically encoded probes, differential photoacoustic tomography (PAT) enables deep-tissue imaging with high resolution and sensitivity; however, current bacteriophytochrome-based probes are bulky multidomain proteins exceeding 55 kDa, which constrains their use for designing PAT molecular reporters. Here we engineer rsmiRFPnano, a compact cyanobacteriochrome-derived photoswitchable PAT probe. With a molecular weight below 19 kDa, rsmiRFPnano efficiently incorporates biliverdin, exhibits high extinction coefficients in both photochromic states and demonstrates robust performance in live cells. We established rsmiRFPnano-based reporters for NF-κB and AP-1 pathways, which display low basal activity and strong activation-dependent responses. These reporters effectively visualized acute inflammation using noninvasive PAT in vivo, further validated through cellular-level spatial omics mapping. We then created photoswitchable nanobody probes, rsNIR-Fbs, stabilized upon antigen binding and rapidly degraded otherwise, enabling selective photoacoustic immuno-imaging of intracellular antigens in vivo. Together, these results establish rsmiRFPnano as an ultracompact and versatile platform for molecular PAT.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183188","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 : 2026-10-09DOI: 10.1038/s41592-026-03265-w
Daniel S Terry, Roman Kiselev, Manuel F Juette, Zeliha Kilic, Ryan A Brady, Yuansheng Sun, Scott C Blanchard
{"title":"An integrated open-source acquisition and analysis ecosystem for high-throughput single-molecule imaging.","authors":"Daniel S Terry, Roman Kiselev, Manuel F Juette, Zeliha Kilic, Ryan A Brady, Yuansheng Sun, Scott C Blanchard","doi":"10.1038/s41592-026-03265-w","DOIUrl":"https://doi.org/10.1038/s41592-026-03265-w","url":null,"abstract":"","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148824","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 : 2026-10-08DOI: 10.1038/s41592-026-03254-z
Jacob Schreiber
{"title":"Tangermeme: a toolkit for understanding cis-regulatory logic using deep learning models.","authors":"Jacob Schreiber","doi":"10.1038/s41592-026-03254-z","DOIUrl":"https://doi.org/10.1038/s41592-026-03254-z","url":null,"abstract":"<p><p>Deep learning models have achieved state-of-the-art performance at predicting diverse genomic modalities, yet their promise for biological discovery lies in how they are used after demonstrating their predictive performance. Here we describe the functionality of tangermeme, a highly optimized toolkit for 'everything-but-the-model' when it comes to genomic deep learning, and demonstrate how tangermeme can be used to distill the learned cis-regulatory patterns from models into human-interpretable insights.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137619","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 : 2026-10-07DOI: 10.1038/s41592-026-03257-w
Madhura Mukhopadhyay
{"title":"Recording time via brain organoids","authors":"Madhura Mukhopadhyay","doi":"10.1038/s41592-026-03257-w","DOIUrl":"10.1038/s41592-026-03257-w","url":null,"abstract":"","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 10","pages":"1938-1938"},"PeriodicalIF":28.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092125","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 : 2026-10-07DOI: 10.1038/s41592-026-03261-0
{"title":"How to write a rebuttal letter","authors":"","doi":"10.1038/s41592-026-03261-0","DOIUrl":"10.1038/s41592-026-03261-0","url":null,"abstract":"The rebuttal letter is a vitally important document when revising a manuscript for a journal. Here we discuss how to communicate about your manuscript revisions in the best possible light.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 10","pages":"1919-1919"},"PeriodicalIF":28.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41592-026-03261-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100852","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}