Nature MethodsPub Date : 2025-05-06DOI: 10.1038/s41592-025-02690-7
Jesse S Aaron, Caron A Jacobs, Leonel Malacrida, Antje Keppler, Paul French, Daniel A Fletcher, Christopher Wood, Claire M Brown, Graham D Wright, Satoshi Ogawa, Mahmoud Maina, Teng-Leong Chew
{"title":"Challenges of microscopy technology dissemination to resource-constrained communities.","authors":"Jesse S Aaron, Caron A Jacobs, Leonel Malacrida, Antje Keppler, Paul French, Daniel A Fletcher, Christopher Wood, Claire M Brown, Graham D Wright, Satoshi Ogawa, Mahmoud Maina, Teng-Leong Chew","doi":"10.1038/s41592-025-02690-7","DOIUrl":"https://doi.org/10.1038/s41592-025-02690-7","url":null,"abstract":"","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":36.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034283","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 : 2025-05-05DOI: 10.1038/s41592-025-02680-9
Hanxiao Sun, Bo Lu, Zeyu Zhang, Ye Xiao, Zhe Zhou, Lin Xi, Zhichao Li, Zhe Jiang, Jiayi Zhang, Meng Wang, Cong Liu, Yichen Ma, Jinying Peng, Xiu-Jie Wang, Chengqi Yi
{"title":"Mild and ultrafast GLORI enables absolute quantification of m<sup>6</sup>A methylome from low-input samples.","authors":"Hanxiao Sun, Bo Lu, Zeyu Zhang, Ye Xiao, Zhe Zhou, Lin Xi, Zhichao Li, Zhe Jiang, Jiayi Zhang, Meng Wang, Cong Liu, Yichen Ma, Jinying Peng, Xiu-Jie Wang, Chengqi Yi","doi":"10.1038/s41592-025-02680-9","DOIUrl":"https://doi.org/10.1038/s41592-025-02680-9","url":null,"abstract":"<p><p>Methods for absolute quantification of N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) have emerged as powerful tools in epitranscriptomics. We previously reported GLORI, a chemical-assisted approach to achieve unbiased and precise m<sup>6</sup>A measurement. However, its lengthy reaction time and severe RNA degradation have limited its applicability, particularly for low-input samples. Here, we present two updated GLORI approaches that are ultrafast, mild and enable absolute m<sup>6</sup>A quantification from one to two orders of magnitude less than the RNA starting material: GLORI 2.0 is compatible with RNA from ~10,000 cells and enhances sensitivity for both transcriptome-wide and locus-specific m<sup>6</sup>A detection; GLORI 3.0 further utilizes a reverse transcription-silent carrier RNA to achieve m<sup>6</sup>A quantification from as low as 500-1,000 cells. Using limited RNA from mouse dorsal hippocampus, we reveal a high modification level in synapse-related gene sets. We envision that the updated GLORI methods will greatly expand the applicability of absolute quantification of m<sup>6</sup>A in biology.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":36.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982104","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 : 2025-05-01Epub Date: 2025-05-08DOI: 10.1038/s41592-025-02665-8
Jacob Kæstel-Hansen, Marilina de Sautu, Anand Saminathan, Gustavo Scanavachi, Ricardo F Bango Da Cunha Correia, Annette Juma Nielsen, Sara Vogt Bleshøy, Konstantinos Tsolakidis, Wouter Boomsma, Tomas Kirchhausen, Nikos S Hatzakis
{"title":"Deep learning-assisted analysis of single-particle tracking for automated correlation between diffusion and function.","authors":"Jacob Kæstel-Hansen, Marilina de Sautu, Anand Saminathan, Gustavo Scanavachi, Ricardo F Bango Da Cunha Correia, Annette Juma Nielsen, Sara Vogt Bleshøy, Konstantinos Tsolakidis, Wouter Boomsma, Tomas Kirchhausen, Nikos S Hatzakis","doi":"10.1038/s41592-025-02665-8","DOIUrl":"https://doi.org/10.1038/s41592-025-02665-8","url":null,"abstract":"<p><p>Subcellular diffusion in living systems reflects cellular processes and interactions. Recent advances in optical microscopy allow the tracking of this nanoscale diffusion of individual objects with unprecedented precision. However, the agnostic and automated extraction of functional information from the diffusion of molecules and organelles within the subcellular environment is labor intensive and poses a significant challenge. Here we introduce DeepSPT, a deep learning framework integrated in an analysis software, to interpret the diffusional two- or three-dimensional temporal behavior of objects in a rapid and efficient manner, agnostically. Demonstrating its versatility, we have applied DeepSPT to automated mapping of the early events of viral infections, identifying endosomal organelles, clathrin-coated pits and vesicles among others with F1 scores of 81%, 82% and 95%, respectively, and within seconds instead of weeks. The fact that DeepSPT effectively extracts biological information from diffusion alone illustrates that besides structure, motion encodes function at the molecular and subcellular level.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 5","pages":"1091-1100"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034068","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 : 2025-05-01Epub Date: 2025-04-17DOI: 10.1038/s41592-025-02651-0
Hechen Li, Ziqi Zhang, Michael Squires, Xi Chen, Xiuwei Zhang
{"title":"scMultiSim: simulation of single-cell multi-omics and spatial data guided by gene regulatory networks and cell-cell interactions.","authors":"Hechen Li, Ziqi Zhang, Michael Squires, Xi Chen, Xiuwei Zhang","doi":"10.1038/s41592-025-02651-0","DOIUrl":"https://doi.org/10.1038/s41592-025-02651-0","url":null,"abstract":"<p><p>Simulated single-cell data are essential for designing and evaluating computational methods in the absence of experimental ground truth. Here we present scMultiSim, a comprehensive simulator that generates multimodal single-cell data encompassing gene expression, chromatin accessibility, RNA velocity and spatial cell locations while accounting for the relationships between modalities. Unlike existing tools that focus on limited biological factors, scMultiSim simultaneously models cell identity, gene regulatory networks, cell-cell interactions and chromatin accessibility while incorporating technical noise. Moreover, it allows users to adjust each factor's effect easily. Here we show that scMultiSim generates data with expected biological effects, and demonstrate its applications by benchmarking a wide range of computational tasks, including multimodal and multi-batch data integration, RNA velocity estimation, gene regulatory network inference and cell-cell interaction inference using spatially resolved gene expression data. Compared to existing simulators, scMultiSim can benchmark a much broader range of existing computational problems and even new potential tasks.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 5","pages":"982-993"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028492","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 : 2025-05-01Epub Date: 2025-05-13DOI: 10.1038/s41592-025-02689-0
Naixin Qian, Zhilun Zhao, Elsy El Khoury, Xin Gao, Carli Canela, Yihui Shen, Lingyan Shi, Lixue Shi, Fanghao Hu, Lu Wei, Wei Min
{"title":"Illuminating life processes by vibrational probes.","authors":"Naixin Qian, Zhilun Zhao, Elsy El Khoury, Xin Gao, Carli Canela, Yihui Shen, Lingyan Shi, Lixue Shi, Fanghao Hu, Lu Wei, Wei Min","doi":"10.1038/s41592-025-02689-0","DOIUrl":"https://doi.org/10.1038/s41592-025-02689-0","url":null,"abstract":"<p><p>Vibration of chemical bonds can serve as imaging contrast. Vibrational probes, synergized with major advances in chemical bond imaging instruments, have recently flourished and proven valuable in illuminating life processes. Here, we review how the development of vibrational probes with optimal biocompatibility, enhanced sensitivity, multichromatic colors and diverse functionality has extended chemical bond imaging beyond the prevalent label-free paradigm into various novel applications such as imaging metabolites, metabolic imaging, drug imaging, super-multiplex imaging, vibrational profiling and vibrational sensing. These advancements in vibrational probes have greatly facilitated understanding living systems, a new field of vibrational chemical biology.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 5","pages":"928-944"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030571","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 : 2025-05-01DOI: 10.1038/s41592-025-02714-2
{"title":"Capturing more than meets the eye.","authors":"","doi":"10.1038/s41592-025-02714-2","DOIUrl":"https://doi.org/10.1038/s41592-025-02714-2","url":null,"abstract":"","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 5","pages":"875-876"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972423","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 : 2025-05-01DOI: 10.1038/s41592-025-02616-3
Tao Chen, Marzia Savini, Meng C Wang
{"title":"Unlocking in vivo metabolic insights with vibrational microscopy.","authors":"Tao Chen, Marzia Savini, Meng C Wang","doi":"10.1038/s41592-025-02616-3","DOIUrl":"https://doi.org/10.1038/s41592-025-02616-3","url":null,"abstract":"","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 5","pages":"886-889"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982742","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 : 2025-05-01DOI: 10.1038/s41592-025-02650-1
Xiaoliang Sunney Xie
{"title":"25 years of 3D coherent Raman imaging for biomedicine.","authors":"Xiaoliang Sunney Xie","doi":"10.1038/s41592-025-02650-1","DOIUrl":"https://doi.org/10.1038/s41592-025-02650-1","url":null,"abstract":"","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 5","pages":"877-882"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036414","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 : 2025-05-01Epub Date: 2025-03-28DOI: 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":"<p><p>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.</p>","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}