Nature biotechnology最新文献_第4页

A structurally informed human protein–protein interactome reveals proteome-wide perturbations caused by disease mutations 从结构上了解人类蛋白质-蛋白质相互作用组，揭示疾病突变引起的全蛋白质组扰动

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-24 DOI: 10.1038/s41587-024-02428-4

Dapeng Xiong, Yunguang Qiu, Junfei Zhao, Yadi Zhou, Dongjin Lee, Shobhita Gupta, Mateo Torres, Weiqiang Lu, Siqi Liang, Jin Joo Kang, Charis Eng, Joseph Loscalzo, Feixiong Cheng, Haiyuan Yu

{"title":"A structurally informed human protein–protein interactome reveals proteome-wide perturbations caused by disease mutations","authors":"Dapeng Xiong, Yunguang Qiu, Junfei Zhao, Yadi Zhou, Dongjin Lee, Shobhita Gupta, Mateo Torres, Weiqiang Lu, Siqi Liang, Jin Joo Kang, Charis Eng, Joseph Loscalzo, Feixiong Cheng, Haiyuan Yu","doi":"10.1038/s41587-024-02428-4","DOIUrl":"https://doi.org/10.1038/s41587-024-02428-4","url":null,"abstract":"To assist the translation of genetic findings to disease pathobiology and therapeutics discovery, we present an ensemble deep learning framework, termed PIONEER (Protein–protein InteractiOn iNtErfacE pRediction), that predicts protein-binding partner-specific interfaces for all known protein interactions in humans and seven other common model organisms to generate comprehensive structurally informed protein interactomes. We demonstrate that PIONEER outperforms existing state-of-the-art methods and experimentally validate its predictions. We show that disease-associated mutations are enriched in PIONEER-predicted protein–protein interfaces and explore their impact on disease prognosis and drug responses. We identify 586 significant protein–protein interactions (PPIs) enriched with PIONEER-predicted interface somatic mutations (termed oncoPPIs) from analysis of approximately 11,000 whole exomes across 33 cancer types and show significant associations of oncoPPIs with patient survival and drug responses. PIONEER, implemented as both a web server platform and a software package, identifies functional consequences of disease-associated alleles and offers a deep learning tool for precision medicine at multiscale interactome network levels.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488475","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

Pest control gets the CRISPR treatment 害虫控制得到 CRISPR 处理

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-10-23 DOI: 10.1038/s41587-024-02449-z

Caroline Seydel

引用次数: 0

Droplet Hi-C enables scalable, single-cell profiling of chromatin architecture in heterogeneous tissues 液滴Hi-C可对异质组织的染色质结构进行可扩展的单细胞分析

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-18 DOI: 10.1038/s41587-024-02447-1

Lei Chang, Yang Xie, Brett Taylor, Zhaoning Wang, Jiachen Sun, Ethan J. Armand, Shreya Mishra, Jie Xu, Melodi Tastemel, Audrey Lie, Zane A. Gibbs, Hannah S. Indralingam, Tuyet M. Tan, Rafael Bejar, Clark C. Chen, Frank B. Furnari, Ming Hu, Bing Ren

{"title":"Droplet Hi-C enables scalable, single-cell profiling of chromatin architecture in heterogeneous tissues","authors":"Lei Chang, Yang Xie, Brett Taylor, Zhaoning Wang, Jiachen Sun, Ethan J. Armand, Shreya Mishra, Jie Xu, Melodi Tastemel, Audrey Lie, Zane A. Gibbs, Hannah S. Indralingam, Tuyet M. Tan, Rafael Bejar, Clark C. Chen, Frank B. Furnari, Ming Hu, Bing Ren","doi":"10.1038/s41587-024-02447-1","DOIUrl":"https://doi.org/10.1038/s41587-024-02447-1","url":null,"abstract":"Current methods for analyzing chromatin architecture are not readily scalable to heterogeneous tissues. Here we introduce Droplet Hi-C, which uses a commercial microfluidic device for high-throughput, single-cell chromatin conformation profiling in droplets. Using Droplet Hi-C, we mapped the chromatin architecture of the mouse cortex and analyzed gene regulatory programs in major cortical cell types. In addition, we used this technique to detect copy number variations, structural variations and extrachromosomal DNA in human glioblastoma, colorectal and blood cancer cells, revealing clonal dynamics and other oncogenic events during treatment. We refined the technique to allow joint profiling of chromatin architecture and transcriptome in single cells, facilitating exploration of the links between chromatin architecture and gene expression in both normal tissues and tumors. Thus, Droplet Hi-C both addresses critical gaps in chromatin analysis of heterogeneous tissues and enhances understanding of gene regulation.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448119","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

Global profiling of protein complex dynamics with an experimental library of protein interaction markers 利用蛋白质相互作用标记实验库全面剖析蛋白质复合物动态

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-16 DOI: 10.1038/s41587-024-02432-8

Christian Dörig, Cathy Marulli, Thomas Peskett, Norbert Volkmar, Lorenzo Pantolini, Gabriel Studer, Camilla Paleari, Fabian Frommelt, Torsten Schwede, Natalie de Souza, Yves Barral, Paola Picotti

{"title":"Global profiling of protein complex dynamics with an experimental library of protein interaction markers","authors":"Christian Dörig, Cathy Marulli, Thomas Peskett, Norbert Volkmar, Lorenzo Pantolini, Gabriel Studer, Camilla Paleari, Fabian Frommelt, Torsten Schwede, Natalie de Souza, Yves Barral, Paola Picotti","doi":"10.1038/s41587-024-02432-8","DOIUrl":"https://doi.org/10.1038/s41587-024-02432-8","url":null,"abstract":"Methods to systematically monitor protein complex dynamics are needed. We introduce serial ultrafiltration combined with limited proteolysis-coupled mass spectrometry (FLiP–MS), a structural proteomics workflow that generates a library of peptide markers specific to changes in PPIs by probing differences in protease susceptibility between complex-bound and monomeric forms of proteins. The library includes markers mapping to protein-binding interfaces and markers reporting on structural changes that accompany PPI changes. Integrating the marker library with LiP–MS data allows for global profiling of protein–protein interactions (PPIs) from unfractionated lysates. We apply FLiP–MS to Saccharomyces cerevisiae and probe changes in protein complex dynamics after DNA replication stress, identifying links between Spt-Ada-Gcn5 acetyltransferase activity and the assembly state of several complexes. FLiP–MS enables protein complex dynamics to be probed on any perturbation, proteome-wide, at high throughput, with peptide-level structural resolution and informing on occupancy of binding interfaces, thus providing both global and molecular views of a system under study.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440263","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

Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR–Cas9 ribonucleoprotein 通过脂质纳米颗粒输送稳定的 CRISPR-Cas9 核糖核蛋白进行肺和肝脏编辑

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2024-10-16 DOI: 10.1038/s41587-024-02437-3

Kai Chen, Hesong Han, Sheng Zhao, Bryant Xu, Boyan Yin, Atip Lawanprasert, Marena Trinidad, Benjamin W. Burgstone, Niren Murthy, Jennifer A. Doudna

{"title":"Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR–Cas9 ribonucleoprotein","authors":"Kai Chen, Hesong Han, Sheng Zhao, Bryant Xu, Boyan Yin, Atip Lawanprasert, Marena Trinidad, Benjamin W. Burgstone, Niren Murthy, Jennifer A. Doudna","doi":"10.1038/s41587-024-02437-3","DOIUrl":"https://doi.org/10.1038/s41587-024-02437-3","url":null,"abstract":"Lipid nanoparticle (LNP) delivery of clustered regularly interspaced short palindromic repeat (CRISPR) ribonucleoproteins (RNPs) could enable high-efficiency, low-toxicity and scalable in vivo genome editing if efficacious RNP–LNP complexes can be reliably produced. Here we engineer a thermostable Cas9 from Geobacillus stearothermophilus (GeoCas9) to generate iGeoCas9 variants capable of >100× more genome editing of cells and organs compared with the native GeoCas9 enzyme. Furthermore, iGeoCas9 RNP–LNP complexes edit a variety of cell types and induce homology-directed repair in cells receiving codelivered single-stranded DNA templates. Using tissue-selective LNP formulations, we observe genome-editing levels of 16‒37% in the liver and lungs of reporter mice that receive single intravenous injections of iGeoCas9 RNP–LNPs. In addition, iGeoCas9 RNPs complexed to biodegradable LNPs edit the disease-causing SFTPC gene in lung tissue with 19% average efficiency, representing a major improvement over genome-editing levels observed previously using viral or nonviral delivery strategies. These results show that thermostable Cas9 RNP–LNP complexes can expand the therapeutic potential of genome editing.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440260","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

People 人

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-10-14 DOI: 10.1038/s41587-024-02421-x

引用次数: 0

The global patent landscape of functional food innovation 功能性食品创新的全球专利格局

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-10-14 DOI: 10.1038/s41587-024-02410-0

Maima Matin, Dalibor Hrg, Olena Litvinova, Małgorzata Łysek-Gładysinska, Agnieszka Wierzbicka, Jarosław Olav Horbańczuk, Artur Jóźwik, Atanas G. Atanasov

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The European Innovation Council supports innovative portfolios in health biotech 欧洲创新理事会支持健康生物技术领域的创新组合

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-10-14 DOI: 10.1038/s41587-024-02416-8

Iordanis Arzimanoglou

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Biotech news from around the world 全球生物技术新闻

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-10-14 DOI: 10.1038/s41587-024-02436-4

引用次数: 0

Accessible training for academic clinicians and researchers to address the need for academic entrepreneurs 为学术临床医生和研究人员提供可获得的培训，以满足学术创业者的需求

IF 33.1 1区生物学

Nature biotechnology Pub Date : 2024-10-14 DOI: 10.1038/s41587-024-02417-7

Victoria Bartek, Daria Ferro, Flaura Winston, Mark Kessel

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