Pub Date : 2025-12-08DOI: 10.1038/s41592-025-02984-w
Mary Melissa Roland, Alok V. Joglekar
TIRTL-seq is an innovative method that allows efficient and cost-effective identification of αβ TCR clones from millions of T cells with the aid of a pairing algorithm called T-SHELL, which provides high accuracy and throughput in sequencing paired TCR clones.
{"title":"TIRTL-seq: heroes with T-SHELL","authors":"Mary Melissa Roland, Alok V. Joglekar","doi":"10.1038/s41592-025-02984-w","DOIUrl":"10.1038/s41592-025-02984-w","url":null,"abstract":"TIRTL-seq is an innovative method that allows efficient and cost-effective identification of αβ TCR clones from millions of T cells with the aid of a pairing algorithm called T-SHELL, which provides high accuracy and throughput in sequencing paired TCR clones.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 1","pages":"16-17"},"PeriodicalIF":32.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708717","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 : 2025-12-08DOI: 10.1038/s41592-025-02943-5
Ramin Khajeh, Wei-Chung Allen Lee
Connectomics, the comprehensive mapping of neural circuits at nanoscale resolution, has historically relied on electron microscopy (EM), both transmission (TEM) and scanning (SEM). However, as connectomics scales towards larger brain volumes and whole mammalian brains, substantial technical challenges emerge. Here, we highlight key challenges and advancing approaches that hold promise, particularly those that integrate three-dimensional, multi-resolution and time-resolved imaging to capture both long-range and local wiring, down to supramolecular resolution.
{"title":"Connectomics beyond electron microscopy","authors":"Ramin Khajeh, Wei-Chung Allen Lee","doi":"10.1038/s41592-025-02943-5","DOIUrl":"10.1038/s41592-025-02943-5","url":null,"abstract":"Connectomics, the comprehensive mapping of neural circuits at nanoscale resolution, has historically relied on electron microscopy (EM), both transmission (TEM) and scanning (SEM). However, as connectomics scales towards larger brain volumes and whole mammalian brains, substantial technical challenges emerge. Here, we highlight key challenges and advancing approaches that hold promise, particularly those that integrate three-dimensional, multi-resolution and time-resolved imaging to capture both long-range and local wiring, down to supramolecular resolution.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 12","pages":"2487-2489"},"PeriodicalIF":32.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708615","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 : 2025-12-08DOI: 10.1038/s41592-025-02957-z
Lei Tang
Protein editors complement genome editing tools by enabling direct modifications to protein molecules.
蛋白质编辑器通过直接修改蛋白质分子来补充基因组编辑工具。
{"title":"Protein editing","authors":"Lei Tang","doi":"10.1038/s41592-025-02957-z","DOIUrl":"10.1038/s41592-025-02957-z","url":null,"abstract":"Protein editors complement genome editing tools by enabling direct modifications to protein molecules.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 12","pages":"2496-2496"},"PeriodicalIF":32.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708694","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 : 2025-12-08DOI: 10.1038/s41592-025-02951-5
Lin Tang
Virtual cells based on artificial intelligence models are on the horizon
基于人工智能模型的虚拟细胞即将出现
{"title":"The virtual cell","authors":"Lin Tang","doi":"10.1038/s41592-025-02951-5","DOIUrl":"10.1038/s41592-025-02951-5","url":null,"abstract":"Virtual cells based on artificial intelligence models are on the horizon","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 12","pages":"2493-2493"},"PeriodicalIF":32.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708763","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 : 2025-12-08DOI: 10.1038/s41592-025-02955-1
Nina Vogt
Extracellular recordings provide a wealth of information about neuronal activity but it is difficult to link this information to cell types.
细胞外记录提供了大量关于神经元活动的信息，但很难将这些信息与细胞类型联系起来。
{"title":"Cell typing by electrophysiology","authors":"Nina Vogt","doi":"10.1038/s41592-025-02955-1","DOIUrl":"10.1038/s41592-025-02955-1","url":null,"abstract":"Extracellular recordings provide a wealth of information about neuronal activity but it is difficult to link this information to cell types.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 12","pages":"2495-2496"},"PeriodicalIF":32.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708624","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 : 2025-12-08DOI: 10.1038/s41592-025-02941-7
Moritz Helmstaedter
Connectomics has so far outpaced the Moore’s law predictions about technological progress. At this pace, many whole-brain connectomes and connectomic screening will soon be realistic.
{"title":"Optimism for abundant whole-brain connectomes and connectomic screening","authors":"Moritz Helmstaedter","doi":"10.1038/s41592-025-02941-7","DOIUrl":"10.1038/s41592-025-02941-7","url":null,"abstract":"Connectomics has so far outpaced the Moore’s law predictions about technological progress. At this pace, many whole-brain connectomes and connectomic screening will soon be realistic.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 12","pages":"2490-2492"},"PeriodicalIF":32.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708706","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 : 2025-12-08DOI: 10.1038/s41592-025-02956-0
Lei Tang
Experimental and computational advances have improved enhancer characterization and design.
实验和计算的进步改进了增强子的特性和设计。
{"title":"Understanding enhancer logic through synthetic design","authors":"Lei Tang","doi":"10.1038/s41592-025-02956-0","DOIUrl":"10.1038/s41592-025-02956-0","url":null,"abstract":"Experimental and computational advances have improved enhancer characterization and design.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 12","pages":"2494-2495"},"PeriodicalIF":32.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708709","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 : 2025-12-08DOI: 10.1038/s41592-025-02988-6
A large network of interconnected neurons serves as the basis of brain function and of behavior. Methodological advances have enabled the reconstruction of large-scale and even whole-brain connectomes of various organisms.
{"title":"Method of the Year 2025: electron microscopy-based connectomics","authors":"","doi":"10.1038/s41592-025-02988-6","DOIUrl":"10.1038/s41592-025-02988-6","url":null,"abstract":"A large network of interconnected neurons serves as the basis of brain function and of behavior. Methodological advances have enabled the reconstruction of large-scale and even whole-brain connectomes of various organisms.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 12","pages":"2463-2464"},"PeriodicalIF":32.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41592-025-02988-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708581","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 : 2025-12-08DOI: 10.1038/s41592-025-02958-y
Lin Tang
Artificial intelligence agents may have a transformative effect on how biological research is performed.
人工智能代理可能会对生物研究的进行方式产生变革性的影响。
{"title":"Artificial intelligence agents for biology","authors":"Lin Tang","doi":"10.1038/s41592-025-02958-y","DOIUrl":"10.1038/s41592-025-02958-y","url":null,"abstract":"Artificial intelligence agents may have a transformative effect on how biological research is performed.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 12","pages":"2496-2497"},"PeriodicalIF":32.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708595","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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