Nature biotechnology最新文献_第8页

Engineering mitochondrial DNA deletions in human cells improves disease modeling 人体细胞线粒体 DNA 基因缺失工程改善了疾病建模

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-14 DOI: 10.1038/s41587-025-02652-6

Iris Marchal

{"title":"Engineering mitochondrial DNA deletions in human cells improves disease modeling","authors":"Iris Marchal","doi":"10.1038/s41587-025-02652-6","DOIUrl":"https://doi.org/10.1038/s41587-025-02652-6","url":null,"abstract":"Genetically modifying human mitochondrial DNA (mtDNA) is challenging when generating large-scale deletions — a common cause of mitochondrial diseases — owing to the absence of double strand break repair machinery in mitochondria. Writing in Cell, Fu et al. describe a method to modulate large mtDNA deletions in human cells by co-expressing end-joining machinery from Mycobacterium or T4 bacteriophage with targeted endonucleases, providing insights into the underlying mechanisms of mitochondrial disease.The presence of both normal and mutated mtDNA within cells, known as heteroplasmy, is decisive in mitochondrial disease as the proportion of mutated mtDNA dictates the severity of disease manifestation. To model mtDNA deletions at defined heteroplasmy levels, the authors co-expressed end-joining machinery with the restriction enzyme Scal in epithelial cells, resulting in a panel of cells with mtDNA deletions of around 3.5 kilobases. In-depth characterization of these cells revealed a critical threshold of about 75% heteroplasmy, beyond which cells showed impaired oxidative phosphorylation and reduced cell growth with a loss of TCA cycle metabolites and aspartate levels. Single-cell sequencing detected two nuclear gene expression programs that were deregulated with increased heteroplasmy, revealing a threshold-triggered response and a gradual heteroplasmy-sensing network. The functional relevance of such gene network disruptions should be studied further.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"6 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831821","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}

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Engineering innate immune cells for cancer immunotherapy 先天免疫细胞工程用于癌症免疫疗法

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-14 DOI: 10.1038/s41587-025-02629-5

Mubin Tarannum, Xizhong Ding, Marta Barisa, Sabrina Hu, John Anderson, Rizwan Romee, Jin Zhang

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Virtual cells for predictive immunotherapy 用于预测性免疫疗法的虚拟细胞

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-14 DOI: 10.1038/s41587-025-02583-2

Daniel R. Bergman, Elana J. Fertig

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Mismatch repair inhibitors lift off in Huntington’s 错配修复抑制剂在亨廷顿氏症中大显身手

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-14 DOI: 10.1038/s41587-025-02646-4

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Putting cancer immunotherapy into spatial context in the clinic 将癌症免疫疗法与临床空间环境相结合

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-14 DOI: 10.1038/s41587-025-02596-x

Camilla Engblom, Joakim Lundeberg

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Mapping the patent landscape of TROP2-targeted biologics through deep learning 通过深度学习绘制trop2靶向生物制剂的专利版图

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-14 DOI: 10.1038/s41587-025-02626-8

Yu Xiang, Yuyang Jin, Kunmeng Liu, Benzheng Wei

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FDA approves Alnylam’s anti-amyloid RNAi drug for cardiomyopathy FDA 批准 Alnylam 的抗淀粉样蛋白 RNAi 药物治疗心肌病

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-14 DOI: 10.1038/s41587-025-02656-2

引用次数: 0

Hyperspectral reporters for long-distance and wide-area detection of gene expression in living bacteria 用于远距离和大范围检测活细菌基因表达的高光谱报告器

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-11 DOI: 10.1038/s41587-025-02622-y

Yonatan Chemla, Itai Levin, Yueyang Fan, Anna A. Johnson, Connor W. Coley, Christopher A. Voigt

{"title":"Hyperspectral reporters for long-distance and wide-area detection of gene expression in living bacteria","authors":"Yonatan Chemla, Itai Levin, Yueyang Fan, Anna A. Johnson, Connor W. Coley, Christopher A. Voigt","doi":"10.1038/s41587-025-02622-y","DOIUrl":"https://doi.org/10.1038/s41587-025-02622-y","url":null,"abstract":"Genetically encoded reporters are suitable for short-distance imaging in the laboratory but not for scanning wide outdoor areas from a distance. Here we introduce hyperspectral reporters (HSRs) designed for hyperspectral imaging cameras that are commonly mounted on unmanned aerial vehicles and satellites. HSR genes encode enzymes that produce a molecule with a unique absorption signature that can be reliably distinguished in hyperspectral images. Quantum mechanical simulations of 20,170 metabolites identified candidate HSRs, leading to the selection of biliverdin IXα and bacteriochlorophyll a for their distinct absorption spectra and biosynthetic feasibility. These genes were integrated into chemical sensor circuits in soil (Pseudomonas putida) and aquatic (Rubrivivax gelatinosus) bacteria. The bacteria were detectable outdoors under ambient light from up to 90 m in a single 4,000-m2 hyperspectral image taken using fixed and unmanned aerial vehicle-mounted cameras. The dose–response functions of the chemical sensors were measured remotely. HSRs enable large-scale studies and applications in ecology, agriculture, environmental monitoring, forensics and defense.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"16 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819378","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

Severus detects somatic structural variation and complex rearrangements in cancer genomes using long-read sequencing Severus利用长读测序技术检测癌症基因组中的体细胞结构变异和复杂重排

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-04 DOI: 10.1038/s41587-025-02618-8

Ayse G. Keskus, Asher Bryant, Tanveer Ahmad, Byunggil Yoo, Sergey Aganezov, Anton Goretsky, Ataberk Donmez, Lisa A. Lansdon, Isabel Rodriguez, Jimin Park, Yuelin Liu, Xiwen Cui, Joshua Gardner, Brandy McNulty, Samuel Sacco, Jyoti Shetty, Yongmei Zhao, Bao Tran, Giuseppe Narzisi, Adrienne Helland, Daniel E. Cook, Pi-Chuan Chang, Alexey Kolesnikov, Andrew Carroll, Erin K. Molloy, Chengpeng Bi, Adam Walter, Margaret Gibson, Irina Pushel, Erin Guest, Tomi Pastinen, Kishwar Shafin, Karen H. Miga, Salem Malikic, Chi-Ping Day, Nicolas Robine, Cenk Sahinalp, Michael Dean, Midhat S. Farooqi, Benedict Paten, Mikhail Kolmogorov

{"title":"Severus detects somatic structural variation and complex rearrangements in cancer genomes using long-read sequencing","authors":"Ayse G. Keskus, Asher Bryant, Tanveer Ahmad, Byunggil Yoo, Sergey Aganezov, Anton Goretsky, Ataberk Donmez, Lisa A. Lansdon, Isabel Rodriguez, Jimin Park, Yuelin Liu, Xiwen Cui, Joshua Gardner, Brandy McNulty, Samuel Sacco, Jyoti Shetty, Yongmei Zhao, Bao Tran, Giuseppe Narzisi, Adrienne Helland, Daniel E. Cook, Pi-Chuan Chang, Alexey Kolesnikov, Andrew Carroll, Erin K. Molloy, Chengpeng Bi, Adam Walter, Margaret Gibson, Irina Pushel, Erin Guest, Tomi Pastinen, Kishwar Shafin, Karen H. Miga, Salem Malikic, Chi-Ping Day, Nicolas Robine, Cenk Sahinalp, Michael Dean, Midhat S. Farooqi, Benedict Paten, Mikhail Kolmogorov","doi":"10.1038/s41587-025-02618-8","DOIUrl":"https://doi.org/10.1038/s41587-025-02618-8","url":null,"abstract":"For the detection of somatic structural variation (SV) in cancer genomes, long-read sequencing is advantageous over short-read sequencing with respect to mappability and variant phasing. However, most current long-read SV detection methods are not developed for the analysis of tumor genomes characterized by complex rearrangements and heterogeneity. Here, we present Severus, a breakpoint graph-based algorithm for somatic SV calling from long-read cancer sequencing. Severus works with matching normal samples, supports unbalanced cancer karyotypes, can characterize complex multibreak SV patterns and produces haplotype-specific calls. On a comprehensive multitechnology cell line panel, Severus consistently outperforms other long-read and short-read methods in terms of SV detection F1 score (harmonic mean of the precision and recall). We also illustrate that compared to long-read methods, short-read sequencing systematically misses certain classes of somatic SVs, such as insertions or clustered rearrangements. We apply Severus to several clinical cases of pediatric leukemia/lymphoma, revealing clinically relevant cryptic rearrangements missed by standard genomic panels.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"183 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775369","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}

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Scalable spatial transcriptomics through computational array reconstruction 通过计算阵列重建实现可扩展的空间转录组学

IF 46.9 1区生物学

Nature biotechnology Pub Date : 2025-04-03 DOI: 10.1038/s41587-025-02612-0

Chenlei Hu, Mehdi Borji, Giovanni J. Marrero, Vipin Kumar, Jackson A. Weir, Sachin V. Kammula, Evan Z. Macosko, Fei Chen

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