Nature Methods最新文献_第9页

Pooled CRISPR screening with optical sequencing reveals regulators of 3D chromatin organization. 光学测序的CRISPR筛选揭示了三维染色质组织的调节因子。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 DOI: 10.1038/s41592-025-02633-2

Mazhar Adli

引用次数: 0

Denoising Search doubles the number of metabolite and exposome annotations in human plasma using an Orbitrap Astral mass spectrometer. 使用Orbitrap星质谱计，降噪搜索使人类血浆中代谢物和暴露注释的数量加倍。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 Epub Date: 2025-03-28 DOI: 10.1038/s41592-025-02646-x

Fanzhou Kong, Tong Shen, Yuanyue Li, Amer Bashar, Susan S Bird, Oliver Fiehn

{"title":"Denoising Search doubles the number of metabolite and exposome annotations in human plasma using an Orbitrap Astral mass spectrometer.","authors":"Fanzhou Kong, Tong Shen, Yuanyue Li, Amer Bashar, Susan S Bird, Oliver Fiehn","doi":"10.1038/s41592-025-02646-x","DOIUrl":"10.1038/s41592-025-02646-x","url":null,"abstract":"Chemical exposures may affect human metabolism and contribute to the etiology of neurodegenerative disorders such as Alzheimer's disease. Identifying these small metabolites involves matching experimental spectra to reference spectra in databases. However, environmental chemicals or physiologically active metabolites are usually present at low concentrations in human specimens. The presence of noise ions can substantially degrade spectral quality, leading to false negatives and reduced identification rates. In response to this challenge, the Spectral Denoising algorithm removes both chemical and electronic noise. Spectral Denoising outperformed alternative methods in benchmarking studies on 240 tested metabolites. It improved high confident compound identifications at an average 35-fold lower concentrations than previously achievable. Spectral Denoising proved highly robust against varying levels of both chemical and electronic noise even with a greater than 150-fold higher intensity of noise ions than true fragment ions. For human plasma samples from patients with Alzheimer's disease that were analyzed on the Orbitrap Astral mass spectrometer, Denoising Search detected 2.5-fold more annotated compounds compared to the Exploris 240 Orbitrap instrument, including drug metabolites, household and industrial chemicals, and pesticides.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":"1008-1016"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742981","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

25 years of 3D coherent Raman imaging for biomedicine. 25年的生物医学三维相干拉曼成像。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 DOI: 10.1038/s41592-025-02650-1

Xiaoliang Sunney Xie

引用次数: 0

Unlocking in vivo metabolic insights with vibrational microscopy. 用振动显微镜解锁体内代谢的见解。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 DOI: 10.1038/s41592-025-02616-3

Tao Chen, Marzia Savini, Meng C Wang

引用次数: 0

Perturb-tracing enables high-content screening of multi-scale 3D genome regulators. 摄动追踪能够对多尺度3D基因组调控因子进行高含量筛选。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 Epub Date: 2025-04-10 DOI: 10.1038/s41592-025-02652-z

Yubao Cheng, Mengwei Hu, Bing Yang, Tyler B Jensen, Yuan Zhang, Tianqi Yang, Ruihuan Yu, Zhaoxia Ma, Jonathan S D Radda, Shengyan Jin, Chongzhi Zang, Siyuan Wang

{"title":"Perturb-tracing enables high-content screening of multi-scale 3D genome regulators.","authors":"Yubao Cheng, Mengwei Hu, Bing Yang, Tyler B Jensen, Yuan Zhang, Tianqi Yang, Ruihuan Yu, Zhaoxia Ma, Jonathan S D Radda, Shengyan Jin, Chongzhi Zang, Siyuan Wang","doi":"10.1038/s41592-025-02652-z","DOIUrl":"10.1038/s41592-025-02652-z","url":null,"abstract":"Three-dimensional (3D) genome organization becomes altered during development, aging and disease, but the factors regulating chromatin topology are incompletely understood and currently no technology can efficiently screen for new regulators of multi-scale chromatin organization. Here, we developed an image-based high-content screening platform (Perturb-tracing) that combines pooled CRISPR screens, a cellular barcode readout method (BARC-FISH) and chromatin tracing. We performed a loss-of-function screen in human cells, and visualized alterations to their 3D chromatin folding conformations, alongside perturbation-paired barcode readout in the same single cells. We discovered tens of new regulators of chromatin folding at different length scales, ranging from chromatin domains and compartments to chromosome territory. A subset of the regulators exhibited 3D genome effects associated with loop extrusion and A-B compartmentalization mechanisms, while others were largely unrelated to these known 3D genome mechanisms. Finally, we identified new regulators of nuclear architectures and found a functional link between chromatin compaction and nuclear shape. Altogether, our method enables scalable, high-content identification of chromatin and nuclear topology regulators that will stimulate new insights into the 3D genome.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 5","pages":"950-961"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064297","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

CarboTag: a modular approach for live and functional imaging of plant cell walls. CarboTag：一种模块化方法，用于植物细胞壁的活性和功能成像。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 DOI: 10.1038/s41592-025-02677-4

Maarten Besten, Milan Hendriksz, Lucile Michels, Bénédicte Charrier, Elwira Smakowska-Luzan, Dolf Weijers, Jan Willem Borst, Joris Sprakel

引用次数: 0

Scaling a foundational protein language model to 100 billion parameters. 将基础蛋白质语言模型扩展到1000亿个参数。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 DOI: 10.1038/s41592-025-02637-y

引用次数: 0

AI carves out a niche in ecology and conservation research. 人工智能在生态学和自然保护研究中占有一席之地。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 DOI: 10.1038/s41592-025-02682-7

Virginia Gewin

引用次数: 0

Tri-omic single-cell mapping of the 3D epigenome and transcriptome in whole mouse brains throughout the lifespan. 整个小鼠大脑中三维表观基因组和转录组的三组单细胞图谱。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 Epub Date: 2025-04-29 DOI: 10.1038/s41592-025-02658-7

Haoxi Chai, Xingyu Huang, Guangzhou Xiong, Jiaxiang Huang, Katarzyna Karolina Pels, Lingyun Meng, Jin Han, Dongmei Tang, Guanjing Pan, Liang Deng, Qin Xiao, Xiaotao Wang, Meng Zhang, Krzysztof Banecki, Dariusz Plewczynski, Chia-Lin Wei, Yijun Ruan

{"title":"Tri-omic single-cell mapping of the 3D epigenome and transcriptome in whole mouse brains throughout the lifespan.","authors":"Haoxi Chai, Xingyu Huang, Guangzhou Xiong, Jiaxiang Huang, Katarzyna Karolina Pels, Lingyun Meng, Jin Han, Dongmei Tang, Guanjing Pan, Liang Deng, Qin Xiao, Xiaotao Wang, Meng Zhang, Krzysztof Banecki, Dariusz Plewczynski, Chia-Lin Wei, Yijun Ruan","doi":"10.1038/s41592-025-02658-7","DOIUrl":"10.1038/s41592-025-02658-7","url":null,"abstract":"Exploring the genomic basis of transcriptional programs has been a long-standing research focus. Here we report a single-cell method, ChAIR, to map chromatin accessibility, chromatin interactions and RNA expression simultaneously. After validating in cultured cells, we applied ChAIR to whole mouse brains and delineated the concerted dynamics of epigenome, three-dimensional (3D) genome and transcriptome during maturation and aging. In particular, gene-centric chromatin interactions and open chromatin states provided 3D epigenomic mechanism underlying cell-type-specific transcription and revealed spatially resolved specificity. Importantly, the composition of short-range and ultralong chromatin contacts in individual cells is remarkably correlated with transcriptional activity, open chromatin state and genome folding density. This genomic property, along with associated cellular properties, differs in neurons and non-neuronal cells across different anatomic regions throughout the lifespan, implying divergent nuclear mechano-genomic mechanisms at play in brain cells. Our results demonstrate ChAIR's robustness in revealing single-cell 3D epigenomic states of cell-type-specific transcription in complex tissues.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 5","pages":"994-1007"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982105","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

Label-free nanoscopy of cell metabolism by ultrasensitive reweighted visible stimulated Raman scattering. 利用超灵敏重加权可见受激拉曼散射技术进行细胞代谢的无标记纳米观察。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 Epub Date: 2025-01-16 DOI: 10.1038/s41592-024-02575-1

Haonan Lin, Scott Seitz, Yuying Tan, Jean-Baptiste Lugagne, Le Wang, Guangrui Ding, Hongjian He, Tyler J Rauwolf, Mary J Dunlop, John H Connor, John A Porco, Lei Tian, Ji-Xin Cheng

{"title":"Label-free nanoscopy of cell metabolism by ultrasensitive reweighted visible stimulated Raman scattering.","authors":"Haonan Lin, Scott Seitz, Yuying Tan, Jean-Baptiste Lugagne, Le Wang, Guangrui Ding, Hongjian He, Tyler J Rauwolf, Mary J Dunlop, John H Connor, John A Porco, Lei Tian, Ji-Xin Cheng","doi":"10.1038/s41592-024-02575-1","DOIUrl":"10.1038/s41592-024-02575-1","url":null,"abstract":"Super-resolution imaging of cell metabolism is hindered by the incompatibility of small metabolites with fluorescent dyes and the limited resolution of imaging mass spectrometry. We present ultrasensitive reweighted visible stimulated Raman scattering (URV-SRS), a label-free vibrational imaging technique for multiplexed nanoscopy of intracellular metabolites. We developed a visible SRS microscope with extensive pulse chirping to improve the detection limit to ~4,000 molecules and introduced a self-supervised multi-agent denoiser to suppress non-independent noise in SRS by over 7.2 dB, resulting in a 50-fold sensitivity enhancement over near-infrared SRS. Leveraging the enhanced sensitivity, we employed Fourier reweighting to amplify sub-100-nm spatial frequencies that were previously overwhelmed by noise. Validated by Fourier ring correlation, we achieved a lateral resolution of 86 nm in cell imaging. We visualized the reprogramming of metabolic nanostructures associated with virus replication in host cells and subcellular fatty acid synthesis in engineered bacteria, demonstrating its capability towards nanoscopic spatial metabolomics.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":"1040-1050"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008708","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