Nature Biomedical Engineering最新文献_第6页

CRISPR-GPT for agentic automation of gene-editing experiments CRISPR-GPT基因编辑实验的代理自动化

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-30 DOI: 10.1038/s41551-025-01463-z

Yuanhao Qu, Kaixuan Huang, Ming Yin, Kanghong Zhan, Dyllan Liu, Di Yin, Henry C. Cousins, William A. Johnson, Xiaotong Wang, Mihir Shah, Russ B. Altman, Denny Zhou, Mengdi Wang, Le Cong

{"title":"CRISPR-GPT for agentic automation of gene-editing experiments","authors":"Yuanhao Qu, Kaixuan Huang, Ming Yin, Kanghong Zhan, Dyllan Liu, Di Yin, Henry C. Cousins, William A. Johnson, Xiaotong Wang, Mihir Shah, Russ B. Altman, Denny Zhou, Mengdi Wang, Le Cong","doi":"10.1038/s41551-025-01463-z","DOIUrl":"https://doi.org/10.1038/s41551-025-01463-z","url":null,"abstract":"Performing effective gene-editing experiments requires a deep understanding of both the CRISPR technology and the biological system involved. Meanwhile, despite their versatility and promise, large language models (LLMs) often lack domain-specific knowledge and struggle to accurately solve biological design problems. We present CRISPR-GPT, an LLM agent system to automate and enhance CRISPR-based gene-editing design and data analysis. CRISPR-GPT leverages the reasoning capabilities of LLMs for complex task decomposition, decision-making and interactive human–artificial intelligence (AI) collaboration. This system incorporates domain expertise, retrieval techniques, external tools and a specialized LLM fine tuned with open-forum discussions among scientists. CRISPR-GPT assists users in selecting CRISPR systems, experiment planning, designing guide RNAs, choosing delivery methods, drafting protocols, designing assays and analysing data. We showcase the potential of CRISPR-GPT by knocking out four genes with CRISPR-Cas12a in a human lung adenocarcinoma cell line and epigenetically activating two genes using CRISPR-dCas9 in a human melanoma cell line. CRISPR-GPT enables fully AI-guided gene-editing experiment design and analysis across different modalities, validating its effectiveness as an AI co-pilot in genome engineering.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"284 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Non-invasive characterization of pericyte dysfunction in mouse brain using functional ultrasound localization microscopy 应用功能超声定位显微镜无创表征小鼠脑周细胞功能障碍

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-30 DOI: 10.1038/s41551-025-01465-x

Jérémy H. Thalgott, Nicolas Zucker, Thomas Deffieux, Marit S. Koopman, Alexandre Dizeux, Cristina M. Avramut, Roman I. Koning, Hans-Jurgen Mager, Ton J. Rabelink, Mickaël Tanter, Franck Lebrin

{"title":"Non-invasive characterization of pericyte dysfunction in mouse brain using functional ultrasound localization microscopy","authors":"Jérémy H. Thalgott, Nicolas Zucker, Thomas Deffieux, Marit S. Koopman, Alexandre Dizeux, Cristina M. Avramut, Roman I. Koning, Hans-Jurgen Mager, Ton J. Rabelink, Mickaël Tanter, Franck Lebrin","doi":"10.1038/s41551-025-01465-x","DOIUrl":"https://doi.org/10.1038/s41551-025-01465-x","url":null,"abstract":"Early microscopic-scale pericyte dysfunction contributes to the initial stages of many neurological diseases and represents a strong candidate target for therapeutic intervention. A non-invasive imaging modality able to image microvascular alterations induced by pericyte dysfunction is needed. In addition, the development of pericyte-focused therapies remains challenging due to the lack of early biomarkers of disease progression. Here we show that cerebral microvascular alterations induced by pericyte dysfunction can be characterized non-invasively in mice using functional ultrasound localization microscopy (fULM). Depletion of endothelial endoglin in adult mice as a model of hereditary haemorrhagic telangiectasia, leads to pericyte detachment in the arteriole–capillary transition (ACT) zone. Imaging reveals that arteriolar capillaries have irregular shapes, increased diameters, reduced blood speed and neurovascular uncoupling mainly localized in the ACT zone. Transforming growth factor-β signalling activator C381 restores pericyte coverage and neurovascular response. Our study underscores the potential of fULM in characterizing early microvascular alterations. As super-resolution ultrasound transitions to the clinic, our data support its future use in monitoring pericyte-focused therapies in humans.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"130 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Accelerating primer design for amplicon sequencing using large language model-powered agents 使用大型语言模型驱动的代理加速扩增子测序引物设计

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-30 DOI: 10.1038/s41551-025-01455-z

Yi Wang, Yuejie Hou, Lin Yang, Shisen Li, Weiting Tang, Hui Tang, Qiushun He, Siyuan Lin, Yanyan Zhang, Xingyu Li, Shiwen Chen, Yusheng Huang, Lingsong Kong, Huijun Zhang, Duncan Yu, Feng Mu, Huanming Yang, Jian Wang, Nattiya Hirankarn, Meng Yang

{"title":"Accelerating primer design for amplicon sequencing using large language model-powered agents","authors":"Yi Wang, Yuejie Hou, Lin Yang, Shisen Li, Weiting Tang, Hui Tang, Qiushun He, Siyuan Lin, Yanyan Zhang, Xingyu Li, Shiwen Chen, Yusheng Huang, Lingsong Kong, Huijun Zhang, Duncan Yu, Feng Mu, Huanming Yang, Jian Wang, Nattiya Hirankarn, Meng Yang","doi":"10.1038/s41551-025-01455-z","DOIUrl":"https://doi.org/10.1038/s41551-025-01455-z","url":null,"abstract":"The pre-trained knowledge compressed in large language models is addressing diverse scientific challenges and catalysing the progression of autonomous laboratory systems, synergized with liquid handling robots. Here we introduce PrimeGen, an orchestrated multi-agent system powered by large language models, designed to streamline labour-intensive primer design tasks for targeted next-generation sequencing. PrimeGen uses GPT-4o as a central controller to engage with experimentalists for task planning and decomposition, coordinating various specialized agents to execute distinct subtasks. These include an interactive search agent for retrieving gene targets from databases, a primer agent for designing primer sequences across multiple scenarios, a protocol agent for generating executable robot scripts through retrieval-augmented generation and prompt engineering, and an experiment agent equipped with a vision language model for detecting and reporting anomalies. We experimentally demonstrate the effectiveness of PrimeGen across a variety of applications. PrimeGen can accommodate up to 955 amplicons, ensuring high amplification uniformity and minimizing dimer formation. Our development underscores the potential of collaborative agents, coordinated by generalist foundation models, as intelligent tools for advancing biomedical research.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"148 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Osteopontin de-escalates the foreign body response 骨桥蛋白减轻了异物反应

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-30 DOI: 10.1038/s41551-025-01472-y

Sergei Butenko, Maksim V. Plikus

引用次数: 0

Integrated in vivo combinatorial functional genomics and spatial transcriptomics of tumours to decode genotype-to-phenotype relationships 整合体内肿瘤组合功能基因组学和空间转录组学，解码基因型-表型关系

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-28 DOI: 10.1038/s41551-025-01437-1

Marco Breinig, Artem Lomakin, Elyas Heidari, Michael Ritter, Gleb Rukhovich, Lio Böse, Luise Butthof, Lena Wendler-Link, Hendrik Wiethoff, Tanja Poth, Felix Sahm, Peter Schirmacher, Oliver Stegle, Moritz Gerstung, Darjus F. Tschaharganeh

引用次数: 0

Efficient and sustained optogenetic control of sensory and cardiac systems 有效和持续的光遗传控制的感觉和心脏系统

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-28 DOI: 10.1038/s41551-025-01461-1

Alexey Alekseev, Victoria Hunniford, Maria Zerche, Marcus Jeschke, Fadhel El May, Anna Vavakou, Dominique Siegenthaler, Marc A. Hüser, Svenja M. Kiehn, Aida Garrido-Charles, Alexander Meyer, Adrian Rambousky, Theocharis Alvanos, Isabel Witzke, Keila Dara Rojas-Garcia, Martin D. Draband, Lukas Cyganek, Eric Klein, Patrick Ruther, Antoine Huet, Stuart Trenholm, Emilie Macé, Kathrin Kusch, Tobias Bruegmann, Bettina J. Wolf, Thomas Mager, Tobias Moser

{"title":"Efficient and sustained optogenetic control of sensory and cardiac systems","authors":"Alexey Alekseev, Victoria Hunniford, Maria Zerche, Marcus Jeschke, Fadhel El May, Anna Vavakou, Dominique Siegenthaler, Marc A. Hüser, Svenja M. Kiehn, Aida Garrido-Charles, Alexander Meyer, Adrian Rambousky, Theocharis Alvanos, Isabel Witzke, Keila Dara Rojas-Garcia, Martin D. Draband, Lukas Cyganek, Eric Klein, Patrick Ruther, Antoine Huet, Stuart Trenholm, Emilie Macé, Kathrin Kusch, Tobias Bruegmann, Bettina J. Wolf, Thomas Mager, Tobias Moser","doi":"10.1038/s41551-025-01461-1","DOIUrl":"https://doi.org/10.1038/s41551-025-01461-1","url":null,"abstract":"Optogenetic control is used to manipulate the activity of specific cell types in vivo for a variety of biological and clinical applications. Here we report ChReef, an improved variant of the channelrhodopsin ChRmine. ChReef offers minimal photocurrent desensitization, a unitary conductance of 80 fS and closing kinetics of 30 ms, which together enable reliable optogenetic control of cells at low light levels with good temporal fidelity and sustained stimulation. We demonstrate efficient and reliable red-light pacing and depolarization block of ChReef-expressing cardiomyocyte clusters. We used adeno-associated-virus-based gene transfer to express ChReef in retinal ganglion cells, where it restores visual function in blind mice with light sources as weak as an iPad screen. Toward optogenetic hearing restoration, ChReef enables stimulation of the auditory pathway in rodents and non-human primates with nanojoule thresholds, enabling efficient and frequency-specific stimulation by LED-based optical cochlear implants.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"75 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A self-adaptive and versatile tool for eliminating multiple undesirable variations from large-scale transcriptomes 一种自适应和通用的工具，用于消除大规模转录组的多种不希望的变异

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-25 DOI: 10.1038/s41551-025-01466-w

Mengji Zhang, Lei Yan, Xinbo Wang, Yi Yuan, Shimin Zou, Sichao Yao, Xinyu Wang, Bin Chen, Qinghui Li, Zhiyi Zhang, Yin Shan, Yuefan Zhang, Wenjie Wang, Huaixu Zhu, Weibin Song, Tian Xu, Dong Yang

{"title":"A self-adaptive and versatile tool for eliminating multiple undesirable variations from large-scale transcriptomes","authors":"Mengji Zhang, Lei Yan, Xinbo Wang, Yi Yuan, Shimin Zou, Sichao Yao, Xinyu Wang, Bin Chen, Qinghui Li, Zhiyi Zhang, Yin Shan, Yuefan Zhang, Wenjie Wang, Huaixu Zhu, Weibin Song, Tian Xu, Dong Yang","doi":"10.1038/s41551-025-01466-w","DOIUrl":"https://doi.org/10.1038/s41551-025-01466-w","url":null,"abstract":"Accurate identification of true biological signals from diverse undesirable variations in large-scale transcriptomes is essential for downstream discoveries. Here we develop a universal deep neural network, called DeepAdapter, to eliminate various undesirable variations including batch, platform, purity and other unknown sources from transcriptomic data. Our approach automatically learns the corresponding denoising strategies to adapt to different situations. The data-driven strategies are flexible and highly attuned to the transcriptomic data that requires denoising, yielding reduced undesirable variation originating from batches, sequencing platforms and biosamples with varied purity beyond manually designed schemes. Comprehensive evaluations across multiple batches, different RNA measurement technologies and heterogeneous biosamples demonstrate that DeepAdapter can robustly correct diverse undesirable variations and accurately preserve biological signals, the faithful gene expression patterns that facilitate reliable biomarker discovery, transcriptomic network analysis and comprehensive biological characterization. Our findings indicate that DeepAdapter can act as a versatile tool for the comprehensive denoising of the large and heterogeneous transcriptome across a wide variety of application scenarios.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"42 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Harnessing electroencephalography connectomes for cognitive and clinical neuroscience 利用脑电图连接体进行认知和临床神经科学研究

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-23 DOI: 10.1038/s41551-025-01442-4

Yu Zhang, Zhe Sage Chen

{"title":"Harnessing electroencephalography connectomes for cognitive and clinical neuroscience","authors":"Yu Zhang, Zhe Sage Chen","doi":"10.1038/s41551-025-01442-4","DOIUrl":"10.1038/s41551-025-01442-4","url":null,"abstract":"Electroencephalography (EEG) connectomes offer powerful tools for studying brain connectivity and advancing our understanding of brain function and dysfunction in both healthy and pathological conditions. Celebrating the 100th anniversary of EEG discovery, this Perspective explores the frontiers of EEG-based brain connectivity in basic and translational neuroscience research. We review new concepts, emerging analysis frameworks and significant advances in harnessing EEG connectomes. We suggest that leveraging machine learning approaches may offer promising paths to maximize the strengths of EEG connectomes. We also discuss how combined EEG connectome and neuromodulation provide a personalized and adaptive closed-loop paradigm to promote neuroplasticity and treat dysfunctional brains. We further address the limitations and challenges of the current methodology and touch on important issues regarding research rigour and clinical viability for translational impact. This Perspective explores electroencephalography-based connectivity research, highlighting machine learning’s potential and the promise of personalized neuromodulation to enhance neuroplasticity and treat brain dysfunction, while addressing methodological challenges and translational prospects.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 8","pages":"1186-1201"},"PeriodicalIF":26.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic reprogramming with ultrasound-responsive nanovesicles 超声反应纳米囊的代谢重编程

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-22 DOI: 10.1038/s41551-025-01460-2

Jessica C. Hsu, Jingwei Zhou, Weibo Cai

引用次数: 0

Floss-based vaccination targets the gingival sulcus for mucosal and systemic immunization 基于牙线的疫苗接种针对牙龈沟进行粘膜和全身免疫

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2025-07-22 DOI: 10.1038/s41551-025-01451-3

Rohan S. J. Ingrole, Akhilesh Kumar Shakya, Gaurav Joshi, Chang Hyun Lee, Lazar D. Nesovic, Richard W. Compans, Harvinder Singh Gill

{"title":"Floss-based vaccination targets the gingival sulcus for mucosal and systemic immunization","authors":"Rohan S. J. Ingrole, Akhilesh Kumar Shakya, Gaurav Joshi, Chang Hyun Lee, Lazar D. Nesovic, Richard W. Compans, Harvinder Singh Gill","doi":"10.1038/s41551-025-01451-3","DOIUrl":"https://doi.org/10.1038/s41551-025-01451-3","url":null,"abstract":"The oral cavity is an accessible site for vaccination, but its sublingual and buccal sites have limited vaccine uptake. Here we show that flat tape dental floss can deliver vaccines through the junctional epithelium of the gingival sulcus, exploiting its naturally leaky properties. Floss-based vaccination delivered protein, inactivated virus, peptide-presenting immunogenic nanoparticles and messenger RNA. In mice, gold nanoparticles functionalized with a peptide derived from the ectodomain of the transmembrane matrix 2 protein of human influenza virus stimulated local lymph nodes, increased CD4+T cells in lymph nodes, lungs and spleen, and boosted antibody-secreting cells in the bone marrow. Floss-based immunization induced strong and sustained immune activation across multiple organs, robust systemic and mucosal antibody responses, and durable protection against lethal influenza infection, independent of age, food and liquid consumption. Floss-based vaccination was superior to sublingual and comparable with intranasal vaccination. In human participants, fluorescent dye delivered via floss picks effectively reached gingival sulcus, supporting clinical feasibility. These findings establish floss-based vaccination as a simple, needle-free strategy that enhances vaccine delivery and immune activation compared with existing mucosal immunization methods.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"4 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0