Nature Methods最新文献_第4页

SVPG: a pangenome-based structural variant detection approach and rapid augmentation of pangenome graphs with new samples SVPG：一种基于泛基因组的结构变异检测方法和基于新样本的快速增强泛基因组图谱。

IF 28.3 1区生物学

Nature Methods Pub Date : 2026-09-21 DOI: 10.1038/s41592-026-03219-2

Tao Jiang, Heng Hu, Runtian Gao, Shuqi Cao, Zhongjun Jiang, Murong Zhou, Wentao Gao, Shengming Zhou, Guohua Wang

{"title":"SVPG: a pangenome-based structural variant detection approach and rapid augmentation of pangenome graphs with new samples","authors":"Tao Jiang, Heng Hu, Runtian Gao, Shuqi Cao, Zhongjun Jiang, Murong Zhou, Wentao Gao, Shengming Zhou, Guohua Wang","doi":"10.1038/s41592-026-03219-2","DOIUrl":"10.1038/s41592-026-03219-2","url":null,"abstract":"Breakthrough advances in long-read sequencing have opened unprecedented opportunities to study genetic variations through pangenome analysis, yet tools that effectively leverage such frameworks for structural variant (SV) detection remain limited. In addition, efficient construction of pangenome graphs becomes increasingly challenging with the acquisition of larger numbers of samples. Here we present SVPG, an approach that leverages haplotype-resolved pangenome reference for accurate SV detection and rapid pangenome graph augmentation from long-read sequencing data. Compared with state-of-the-art SV callers, SVPG maintained superior overall performance across different sequencing technologies and coverages. SVPG also achieved notable improvements in calling individual-specific SVs, including rare and somatic SVs. Furthermore, in a benchmark involving 20 samples, SVPG accelerated pangenome graph augmentation by nearly tenfold compared with traditional augmentation strategies. These results indicate that SVPG has the potential to improve SV detection and serve as an effective tool, offering new possibilities for advancing pangenomic research. SVPG performs accurate pangenome-facilitated structural variant detection and accelerates pangenome graph augmentation using long-read sequencing data.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 10","pages":"1984-1993"},"PeriodicalIF":28.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41592-026-03219-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017585","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}

引用次数: 0

When a laser beam hits an electron beam 当激光束撞击电子束时。

IF 28.3 1区生物学

Nature Methods Pub Date : 2026-09-16 DOI: 10.1038/s41592-026-03239-y

Vivien Marx

引用次数: 0

Engaging figures 迷人的人物。

IF 28.3 1区生物学

Nature Methods Pub Date : 2026-09-16 DOI: 10.1038/s41592-026-03241-4

Helena Klara Jambor, Fateme Rajabiyazdi, Verena Prantl, Matthias Flotho, Torsten Möller, Cagatay Turkay

引用次数: 0

SPLENDID incorporates continuous genetic ancestry in biobank-scale data to improve polygenic risk prediction across diverse populations SPLENDID将连续遗传祖先纳入生物库规模数据，以改善不同人群的多基因风险预测。

IF 28.3 1区生物学

Nature Methods Pub Date : 2026-09-14 DOI: 10.1038/s41592-026-03235-2

Tony Chen, Haoyu Zhang, Rahul Mazumder, Xihong Lin

{"title":"SPLENDID incorporates continuous genetic ancestry in biobank-scale data to improve polygenic risk prediction across diverse populations","authors":"Tony Chen, Haoyu Zhang, Rahul Mazumder, Xihong Lin","doi":"10.1038/s41592-026-03235-2","DOIUrl":"10.1038/s41592-026-03235-2","url":null,"abstract":"Polygenic risk scores are widely used in disease risk stratification, but their accuracy varies across different ancestries. Recent methods leverage multi-ancestry data to improve accuracy in under-represented populations but require the labeling of individuals by ancestry. This poses practical challenges, given that clinical decisions are typically not based on ancestry, and many individuals may not fit into a pre-specified ancestry group. Here we propose SPLENDID, a penalized regression framework for large-scale individual-level data that models genetic ancestry as a continuum to produce a single prediction model without any ancestry labels. In extensive simulations and analyses in the All of Us Research Program (n = 224,364) and UK Biobank (n = 340,140), we show that SPLENDID significantly improved prediction accuracy over existing methods, particularly for non-European and admixed ancestries. SPLENDID stands as a valuable tool for robust risk prediction across diverse populations, reduced health disparities in genetic research, and fairer clinical implementation. Rather than relying on pre-specified ancestry labels, which often fail to capture the full genetic heterogeneity of diverse populations, SPLENDID treats ancestry as a continuum and improves polygenic risk score (PRS) prediction for biobank-scale datasets.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 10","pages":"1994-2002"},"PeriodicalIF":28.3,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970017","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}

引用次数: 0

CFM: confinement force microscopy—a dynamic, precise and stable microconfiner for traction force microscopy in spatial confinement CFM：约束力显微镜——一种动态、精确、稳定的空间约束牵引力显微镜。

IF 28.3 1区生物学

Nature Methods Pub Date : 2026-09-14 DOI: 10.1038/s41592-026-03216-5

Fatemeh Abbasi, Katharina Rieck, Matthias Brandt, Maja Matis, Eva Kiermaier, Timo Betz

{"title":"CFM: confinement force microscopy—a dynamic, precise and stable microconfiner for traction force microscopy in spatial confinement","authors":"Fatemeh Abbasi, Katharina Rieck, Matthias Brandt, Maja Matis, Eva Kiermaier, Timo Betz","doi":"10.1038/s41592-026-03216-5","DOIUrl":"10.1038/s41592-026-03216-5","url":null,"abstract":"Cells migrating through tissues experience changing physical confinement, yet methods to dynamically control confinement while quantifying the resulting forces remain limited. Here we present a microconfiner platform for live-cell imaging that enables programmable confinement, allowing real-time control over the level, timing and frequency of confinement while measuring traction forces exerted on the microenvironment, a method we term confinement force microscopy (CFM). Using CFM, we find that cells respond to confinement in two phases: a rapid passive stress rise caused by compression of the cell body and nucleus against the substrate, followed by an active stress increase associated with enhanced contractility, intracellular pressure buildup and bleb formation. Bleb expansion can partially relieve pressure and reduce stress on the surroundings. ROCK and myosin II inhibition both reduce stress generation, but with distinct effects on blebbing. Overall, CFM provides a versatile approach to study dynamic mechanical adaptation in tissue-like environments. CFM enables tunable cell confinement for measuring traction forces exerted by single cells and cell aggregates in tissue-mimicking microenvironments.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 10","pages":"2066-2076"},"PeriodicalIF":28.3,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41592-026-03216-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970024","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}

引用次数: 0

An ultralow-background far-red light-responsive optogenetic tool based on an engineered biliverdin-binding domain 一种基于工程胆绿素结合域的超低背景远红光响应光遗传工具

IF 28.3 1区生物学

Nature Methods Pub Date : 2026-09-11 DOI: 10.1038/s41592-026-03223-6

Giang N. T. Le, Lam M. T. Pham, Boyan Xue, Maruti Uppalapati, G. Andrew Woolley

{"title":"An ultralow-background far-red light-responsive optogenetic tool based on an engineered biliverdin-binding domain","authors":"Giang N. T. Le, Lam M. T. Pham, Boyan Xue, Maruti Uppalapati, G. Andrew Woolley","doi":"10.1038/s41592-026-03223-6","DOIUrl":"10.1038/s41592-026-03223-6","url":null,"abstract":"The robustness and broad applicability of an optogenetic tool depends heavily on the properties of the underlying photoreceptor protein and its cognate binding partner—the light-responsive ‘core’. Current red light optogenetic systems for mammalian cells rely on phytochrome-based photoreceptors: large (70-kDa) proteins that act as dimers, enforcing dimerization on attached proteins. Naturally occurring or engineered binding partners can function effectively, but large size, complex interaction, background binding, weak affinity and modest dynamic range remain limiting. Here we developed a small (17-kDa) monomeric biliverdin-binding photoreceptor, FenixS, and a highly selective, high-affinity binder, Ash1 (6 kDa) using structure-based design and directed evolution. Negligible OFF-state binding and a >1,200-fold increase in binding affinity upon 700-nm illumination yield a high-performance, ultralow background core for diverse applications. A FenixS–Ash1-based optogenetic tool for red light activation of transcription in mammalian cells performs robustly without biliverdin supplementation, with head-to-head comparisons confirming its control of gene expression versus established tools. A compact protein pair that heterodimerizes upon red light activation, FenixS and Ash1, is developed for optogenetic applications.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 10","pages":"2087-2098"},"PeriodicalIF":28.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148933466","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}

引用次数: 0

A wireless modular platform for neuro-behavioral recording and closed-loop manipulation in small animals 一种用于小动物神经行为记录和闭环操作的无线模块化平台。

IF 28.3 1区生物学

Nature Methods Pub Date : 2026-09-10 DOI: 10.1038/s41592-026-03220-9

Zifang Zhao, Hongyu Chang, Praveen Paudel, Jaehyo Park, Can Liu, Maria Q. Aurelio, Azahara Oliva, Antonio Fernandez-Ruiz

{"title":"A wireless modular platform for neuro-behavioral recording and closed-loop manipulation in small animals","authors":"Zifang Zhao, Hongyu Chang, Praveen Paudel, Jaehyo Park, Can Liu, Maria Q. Aurelio, Azahara Oliva, Antonio Fernandez-Ruiz","doi":"10.1038/s41592-026-03220-9","DOIUrl":"10.1038/s41592-026-03220-9","url":null,"abstract":"Investigating the neural mechanisms of social group interactions and other naturalistic behaviors in small animals remains limited by current technology. Tethered neural recording systems are incompatible with many of these behaviors, while existing wireless devices for small animals are constrained by weight, bandwidth, recording duration and the lack of closed-loop modulation capabilities. Here we overcome these limitations by developing a Wireless, Interactive, Lightweight Datalogger (WILD) with integrated flexible neural probes, optogenetics, an inertial measurement unit, an ultrasonic microphone and a head-mounted camera. This platform enables simultaneous, long-term recording of neural activity, locomotor variables, vocalizations and eye movements from groups of freely moving mice in both laboratory and outdoor settings. Model-based real-time signal processing detects specific neural events and behavioral motifs to trigger closed-loop neural interventions. By combining multimodal recordings with advanced onboard signal-processing capabilities in a compact device, WILD enables the investigation of neural mechanisms underlying a broad range of natural behaviors in small animals. WILD is a wireless device that can record neuronal activity, perform optogenetic stimulations, record animal movements, record the environment or eye movements via an integrated camera, analyze the data and trigger optogenetic stimulation. This device facilitates studies of brain activity in freely moving animals such as mice, both in the laboratory and under naturalistic conditions.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"23 10","pages":"2099-2109"},"PeriodicalIF":28.3,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930604","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}

引用次数: 0

Wireless neural recordings from groups of mice inside and outside the laboratory 实验室内外老鼠的无线神经记录。

IF 28.3 1区生物学

Nature Methods Pub Date : 2026-09-10 DOI: 10.1038/s41592-026-03221-8

引用次数: 0

Intend to stay, intent on the dream 打算停留，专心于梦想。

IF 28.3 1区生物学

Nature Methods Pub Date : 2026-09-08 DOI: 10.1038/s41592-026-03240-5

Vivien Marx

引用次数: 0

MemBrain v2: an end-to-end tool for the analysis of membranes in cryo-electron tomography. MemBrain v2：一个端到端的工具，用于分析低温电子断层扫描膜。

IF 28.3 1区生物学

Nature Methods Pub Date : 2026-09-08 DOI: 10.1038/s41592-026-03178-8

Lorenz Lamm, Simon Zufferey, Hanyi Zhang, Ricardo D Righetto, Florent Waltz, Wojciech Wietrzynski, Kevin A Yamauchi, Alister Burt, Ye Liu, Antonio Martinez-Sanchez, Sebastian Ziegler, Fabian Isensee, Julia A Schnabel, Benjamin D Engel, Tingying Peng

{"title":"MemBrain v2: an end-to-end tool for the analysis of membranes in cryo-electron tomography.","authors":"Lorenz Lamm, Simon Zufferey, Hanyi Zhang, Ricardo D Righetto, Florent Waltz, Wojciech Wietrzynski, Kevin A Yamauchi, Alister Burt, Ye Liu, Antonio Martinez-Sanchez, Sebastian Ziegler, Fabian Isensee, Julia A Schnabel, Benjamin D Engel, Tingying Peng","doi":"10.1038/s41592-026-03178-8","DOIUrl":"https://doi.org/10.1038/s41592-026-03178-8","url":null,"abstract":"<p><p>Cryo-electron tomography provides unique insights into macromolecular complexes in their native environments, yet membrane analysis remains a major bottleneck due to low signal-to-noise ratios, missing wedge artifacts and the complexity of membrane-associated particles. Existing tools often require extensive manual annotation, struggle with generalization across datasets and lack integrated solutions for segmentation, particle localization and quantitative analysis. We introduce MemBrain v2, a deep-learning-enabled framework that unifies these tasks into a streamlined pipeline. MemBrain-seg leverages a diverse, collaboratively generated training dataset and specialized model training strategies to achieve generalizable membrane segmentation across variable tomographic conditions. MemBrain-pick enables data-efficient localization of membrane-bound particles by integrating geometric constraints with deep learning, reducing the need for extensive manual annotation. MemBrain-stats provides quantitative insights into particle distributions, computing spatial metrics to analyze intramembrane particle organization. MemBrain v2 integrates seamlessly into cryo-electron tomography workflows, providing an accessible and structured approach to membrane analysis.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912321","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}

引用次数: 0