Nature Biomedical Engineering最新文献_第10页

Bidirectional linkage of DNA barcodes for the multiplexed mapping of higher-order protein interactions in cells 双向连接 DNA 条形码，用于绘制细胞中高阶蛋白质相互作用的复用图谱

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-06-19 DOI: 10.1038/s41551-024-01225-3

Yu Liu, Noah R. Sundah, Nicholas R. Y. Ho, Wan Xiang Shen, Yun Xu, Auginia Natalia, Zhonglang Yu, Ju Ee Seet, Ching Wan Chan, Tze Ping Loh, Brian Y. Lim, Huilin Shao

{"title":"Bidirectional linkage of DNA barcodes for the multiplexed mapping of higher-order protein interactions in cells","authors":"Yu Liu, Noah R. Sundah, Nicholas R. Y. Ho, Wan Xiang Shen, Yun Xu, Auginia Natalia, Zhonglang Yu, Ju Ee Seet, Ching Wan Chan, Tze Ping Loh, Brian Y. Lim, Huilin Shao","doi":"10.1038/s41551-024-01225-3","DOIUrl":"10.1038/s41551-024-01225-3","url":null,"abstract":"Capturing the full complexity of the diverse hierarchical interactions in the protein interactome is challenging. Here we report a DNA-barcoding method for the multiplexed mapping of pairwise and higher-order protein interactions and their dynamics within cells. The method leverages antibodies conjugated with barcoded DNA strands that can bidirectionally hybridize and covalently link to linearize closely spaced interactions within individual 3D protein complexes, encoding and decoding the protein constituents and the interactions among them. By mapping protein interactions in cancer cells and normal cells, we found that tumour cells exhibit a larger diversity and abundance of protein complexes with higher-order interactions. In biopsies of human breast-cancer tissue, the method accurately identified the cancer subtype and revealed that higher-order protein interactions are associated with cancer aggressiveness. A method leveraging antibodies conjugated with barcoded DNA strands to linearize closely spaced interactions from individual 3D protein complexes allows for the mapping of pairwise and higher-order protein interactions within cells.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 7","pages":"909-923"},"PeriodicalIF":26.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425401","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 pathologist–AI collaboration framework for enhancing diagnostic accuracies and efficiencies 提高诊断准确性和效率的病理学家-人工智能合作框架

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-06-19 DOI: 10.1038/s41551-024-01223-5

Zhi Huang, Eric Yang, Jeanne Shen, Dita Gratzinger, Frederick Eyerer, Brooke Liang, Jeffrey Nirschl, David Bingham, Alex M. Dussaq, Christian Kunder, Rebecca Rojansky, Aubre Gilbert, Alexandra L. Chang-Graham, Brooke E. Howitt, Ying Liu, Emily E. Ryan, Troy B. Tenney, Xiaoming Zhang, Ann Folkins, Edward J. Fox, Kathleen S. Montine, Thomas J. Montine, James Zou

{"title":"A pathologist–AI collaboration framework for enhancing diagnostic accuracies and efficiencies","authors":"Zhi Huang, Eric Yang, Jeanne Shen, Dita Gratzinger, Frederick Eyerer, Brooke Liang, Jeffrey Nirschl, David Bingham, Alex M. Dussaq, Christian Kunder, Rebecca Rojansky, Aubre Gilbert, Alexandra L. Chang-Graham, Brooke E. Howitt, Ying Liu, Emily E. Ryan, Troy B. Tenney, Xiaoming Zhang, Ann Folkins, Edward J. Fox, Kathleen S. Montine, Thomas J. Montine, James Zou","doi":"10.1038/s41551-024-01223-5","DOIUrl":"https://doi.org/10.1038/s41551-024-01223-5","url":null,"abstract":"In pathology, the deployment of artificial intelligence (AI) in clinical settings is constrained by limitations in data collection and in model transparency and interpretability. Here we describe a digital pathology framework, nuclei.io, that incorporates active learning and human-in-the-loop real-time feedback for the rapid creation of diverse datasets and models. We validate the effectiveness of the framework via two crossover user studies that leveraged collaboration between the AI and the pathologist, including the identification of plasma cells in endometrial biopsies and the detection of colorectal cancer metastasis in lymph nodes. In both studies, nuclei.io yielded considerable diagnostic performance improvements. Collaboration between clinicians and AI will aid digital pathology by enhancing accuracies and efficiencies.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"61 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425486","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

Enhancement of erythropoietic output by Cas9-mediated insertion of a natural variant in haematopoietic stem and progenitor cells 通过 Cas9 介导的天然变体插入造血干细胞和祖细胞，提高红细胞生成量

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-06-17 DOI: 10.1038/s41551-024-01222-6

Sofia E. Luna, Joab Camarena, Jessica P. Hampton, Kiran R. Majeti, Carsten T. Charlesworth, Eric Soupene, Sridhar Selvaraj, Kun Jia, Vivien A. Sheehan, M. Kyle Cromer, Matthew H. Porteus

{"title":"Enhancement of erythropoietic output by Cas9-mediated insertion of a natural variant in haematopoietic stem and progenitor cells","authors":"Sofia E. Luna, Joab Camarena, Jessica P. Hampton, Kiran R. Majeti, Carsten T. Charlesworth, Eric Soupene, Sridhar Selvaraj, Kun Jia, Vivien A. Sheehan, M. Kyle Cromer, Matthew H. Porteus","doi":"10.1038/s41551-024-01222-6","DOIUrl":"https://doi.org/10.1038/s41551-024-01222-6","url":null,"abstract":"Some gene polymorphisms can lead to monogenic diseases, whereas other polymorphisms may confer beneficial traits. A well-characterized example is congenital erythrocytosis—the non-pathogenic hyper-production of red blood cells—that is caused by a truncated erythropoietin receptor. Here we show that Cas9-mediated genome editing in CD34+ human haematopoietic stem and progenitor cells (HSPCs) can recreate the truncated form of the erythropoietin receptor, leading to substantial increases in erythropoietic output. We also show that combining the expression of the cDNA of a truncated erythropoietin receptor with a previously reported genome-editing strategy to fully replace the HBA1 gene with an HBB transgene in HSPCs (to restore normal haemoglobin production in cells with a β-thalassaemia phenotype) gives the edited HSPCs and the healthy red blood cell phenotype a proliferative advantage. Combining knowledge of human genetics with precise genome editing to insert natural human variants into therapeutic cells may facilitate safer and more effective genome-editing therapies for patients with genetic diseases.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"52 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333607","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

The advent of human-assisted peer review by AI 人工智能辅助同行评审的出现。

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-06-12 DOI: 10.1038/s41551-024-01228-0

引用次数: 0

Author Correction: An injectable subcutaneous colon-specific immune niche for the treatment of ulcerative colitis 作者更正：用于治疗溃疡性结肠炎的可注射皮下结肠特异性免疫龛。

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-06-11 DOI: 10.1038/s41551-024-01232-4

Kin Man Au, Justin E. Wilson, Jenny P.-Y. Ting, Andrew Z. Wang

引用次数: 0

Deep-learning-enabled antibiotic discovery through molecular de-extinction 通过分子去灭绝深度学习发现抗生素

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-06-11 DOI: 10.1038/s41551-024-01201-x

Fangping Wan, Marcelo D. T. Torres, Jacqueline Peng, Cesar de la Fuente-Nunez

{"title":"Deep-learning-enabled antibiotic discovery through molecular de-extinction","authors":"Fangping Wan, Marcelo D. T. Torres, Jacqueline Peng, Cesar de la Fuente-Nunez","doi":"10.1038/s41551-024-01201-x","DOIUrl":"10.1038/s41551-024-01201-x","url":null,"abstract":"Molecular de-extinction aims at resurrecting molecules to solve antibiotic resistance and other present-day biological and biomedical problems. Here we show that deep learning can be used to mine the proteomes of all available extinct organisms for the discovery of antibiotic peptides. We trained ensembles of deep-learning models consisting of a peptide-sequence encoder coupled with neural networks for the prediction of antimicrobial activity and used it to mine 10,311,899 peptides. The models predicted 37,176 sequences with broad-spectrum antimicrobial activity, 11,035 of which were not found in extant organisms. We synthesized 69 peptides and experimentally confirmed their activity against bacterial pathogens. Most peptides killed bacteria by depolarizing their cytoplasmic membrane, contrary to known antimicrobial peptides, which tend to target the outer membrane. Notably, lead compounds (including mammuthusin-2 from the woolly mammoth, elephasin-2 from the straight-tusked elephant, hydrodamin-1 from the ancient sea cow, mylodonin-2 from the giant sloth and megalocerin-1 from the extinct giant elk) showed anti-infective activity in mice with skin abscess or thigh infections. Molecular de-extinction aided by deep learning may accelerate the discovery of therapeutic molecules. Deep learning can be used to mine the proteomes of all available extinct organisms for the discovery of compounds with antibiotic properties.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 7","pages":"854-871"},"PeriodicalIF":26.8,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41551-024-01201-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient site-specific integration of large genes in mammalian cells via continuously evolved recombinases and prime editing 通过持续进化的重组酶和素材编辑技术，在哺乳动物细胞中高效整合大基因的特异位点

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-06-10 DOI: 10.1038/s41551-024-01227-1

Smriti Pandey, Xin D. Gao, Nicholas A. Krasnow, Amber McElroy, Y. Allen Tao, Jordyn E. Duby, Benjamin J. Steinbeck, Julia McCreary, Sarah E. Pierce, Jakub Tolar, Torsten B. Meissner, Elliot L. Chaikof, Mark J. Osborn, David R. Liu

{"title":"Efficient site-specific integration of large genes in mammalian cells via continuously evolved recombinases and prime editing","authors":"Smriti Pandey, Xin D. Gao, Nicholas A. Krasnow, Amber McElroy, Y. Allen Tao, Jordyn E. Duby, Benjamin J. Steinbeck, Julia McCreary, Sarah E. Pierce, Jakub Tolar, Torsten B. Meissner, Elliot L. Chaikof, Mark J. Osborn, David R. Liu","doi":"10.1038/s41551-024-01227-1","DOIUrl":"https://doi.org/10.1038/s41551-024-01227-1","url":null,"abstract":"Methods for the targeted integration of genes in mammalian genomes suffer from low programmability, low efficiencies or low specificities. Here we show that phage-assisted continuous evolution enhances prime-editing-assisted site-specific integrase gene editing (PASSIGE), which couples the programmability of prime editing with the ability of recombinases to precisely integrate large DNA cargoes exceeding 10 kilobases. Evolved and engineered Bxb1 recombinase variants (evoBxb1 and eeBxb1) mediated up to 60% donor integration (3.2-fold that of wild-type Bxb1) in human cell lines with pre-installed recombinase landing sites. In single-transfection experiments at safe-harbour and therapeutically relevant sites, PASSIGE with eeBxb1 led to an average targeted-gene-integration efficiencies of 23% (4.2-fold that of wild-type Bxb1). Notably, integration efficiencies exceeded 30% at multiple sites in primary human fibroblasts. PASSIGE with evoBxb1 or eeBxb1 outperformed PASTE (for ‘programmable addition via site-specific targeting elements’, a method that uses prime editors fused to recombinases) on average by 9.1-fold and 16-fold, respectively. PASSIGE with continuously evolved recombinases is an unusually efficient method for the targeted integration of genes in mammalian cells.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"26 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299018","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

Reinforcement of the intestinal mucosal barrier via mucus-penetrating PEGylated bacteria 通过粘液穿透性聚乙二醇化细菌强化肠粘膜屏障

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-06-05 DOI: 10.1038/s41551-024-01224-4

Yanmei Chen, Sisi Lin, Lu Wang, Yifan Zhang, Huan Chen, Zhenzhen Fu, Mengmeng Zhang, Huilong Luo, Jinyao Liu

{"title":"Reinforcement of the intestinal mucosal barrier via mucus-penetrating PEGylated bacteria","authors":"Yanmei Chen, Sisi Lin, Lu Wang, Yifan Zhang, Huan Chen, Zhenzhen Fu, Mengmeng Zhang, Huilong Luo, Jinyao Liu","doi":"10.1038/s41551-024-01224-4","DOIUrl":"10.1038/s41551-024-01224-4","url":null,"abstract":"The breakdown of the gut’s mucosal barrier that prevents the infiltration of microorganisms, inflammatory cytokines and toxins into bodily tissues can lead to inflammatory bowel disease and to metabolic and autoimmune diseases. Here we show that the intestinal mucosal barrier can be reinforced via the oral administration of commensal bacteria coated with poly(ethylene glycol) (PEG) to facilitate their penetration into mucus. In mice with intestinal homoeostatic imbalance, mucus-penetrating PEGylated bacteria preferentially localized in mucus at the lower gastrointestinal tract, inhibited the invasion of pathogenic bacteria, maintained homoeostasis of the gut microbiota, stimulated the secretion of mucus and the expression of tight junctions, and prevented the mice from developing colitis and diabetes. Orally delivered PEGylated bacteria may help prevent and treat gastrointestinal disorders. The intestinal mucosal barrier can be reinforced via the oral administration of commensal bacteria coated with poly(ethylene glycol) to facilitate their penetration into mucus.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 7","pages":"823-841"},"PeriodicalIF":26.8,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141251583","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 high-density microfluidic bioreactor for the automated manufacturing of CAR T cells 用于自动制造 CAR T 细胞的高密度微流控生物反应器

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-06-04 DOI: 10.1038/s41551-024-01219-1

Wei-Xiang Sin, N. Suhas Jagannathan, Denise Bei Lin Teo, Faris Kairi, Shin Yie Fong, Joel Heng Loong Tan, Dedy Sandikin, Ka-Wai Cheung, Yen Hoon Luah, Xiaolin Wu, Joshua Jebaraj Raymond, Francesca Lorraine Wei Inng Lim, Yie Hou Lee, Michaela Su-Fern Seng, Shui Yen Soh, Qingfeng Chen, Rajeev J. Ram, Lisa Tucker-Kellogg, Michael E. Birnbaum

{"title":"A high-density microfluidic bioreactor for the automated manufacturing of CAR T cells","authors":"Wei-Xiang Sin, N. Suhas Jagannathan, Denise Bei Lin Teo, Faris Kairi, Shin Yie Fong, Joel Heng Loong Tan, Dedy Sandikin, Ka-Wai Cheung, Yen Hoon Luah, Xiaolin Wu, Joshua Jebaraj Raymond, Francesca Lorraine Wei Inng Lim, Yie Hou Lee, Michaela Su-Fern Seng, Shui Yen Soh, Qingfeng Chen, Rajeev J. Ram, Lisa Tucker-Kellogg, Michael E. Birnbaum","doi":"10.1038/s41551-024-01219-1","DOIUrl":"https://doi.org/10.1038/s41551-024-01219-1","url":null,"abstract":"The manufacturing of autologous chimaeric antigen receptor (CAR) T cells largely relies either on fed-batch and manual processes that often lack environmental monitoring and control or on bioreactors that cannot be easily scaled out to meet patient demands. Here we show that human primary T cells can be activated, transduced and expanded to high densities in a 2 ml automated closed-system microfluidic bioreactor to produce viable anti-CD19 CAR T cells (specifically, more than 60 million CAR T cells from donor cells derived from patients with lymphoma and more than 200 million CAR T cells from healthy donors). The in vitro secretion of cytokines, the short-term cytotoxic activity and the long-term persistence and proliferation of the cell products, as well as their in vivo anti-leukaemic activity, were comparable to those of T cells produced in a gas-permeable well. The manufacturing-process intensification enabled by the miniaturized perfusable bioreactor may facilitate the analysis of the growth and metabolic states of CAR T cells during ex vivo culture, the high-throughput optimization of cell-manufacturing processes and the scale out of cell-therapy manufacturing.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"27 17 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246548","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

Structure-guided discovery of highly efficient cytidine deaminases with sequence-context independence 在结构引导下发现与序列上下文无关的高效胞苷脱氨酶

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-06-03 DOI: 10.1038/s41551-024-01220-8

Kui Xu, Hu Feng, Haihang Zhang, Chenfei He, Huifang Kang, Tanglong Yuan, Lei Shi, Chikai Zhou, Guoying Hua, Yaqi Cao, Zhenrui Zuo, Erwei Zuo

引用次数: 0