Samuel J. Lovat, Roee Ben-Nissan, Eliya Milshtein, Asaf Tzachor, Avi Flamholz, Dorian Leger, Elad Noor, Ron Milo
{"title":"Electro-microbial production techno-economic viability and environmental implications","authors":"Samuel J. Lovat, Roee Ben-Nissan, Eliya Milshtein, Asaf Tzachor, Avi Flamholz, Dorian Leger, Elad Noor, Ron Milo","doi":"10.1038/s41587-025-02632-w","DOIUrl":"https://doi.org/10.1038/s41587-025-02632-w","url":null,"abstract":"Producing goods, such as foods and fuels, with minimal environmental impacts is urgently needed. Although advances in bioproduction are promising, there is often a noticeable gap in our understanding of whether and where new processes can compete with existing methods on an economic and environmental basis. Transparent lower bound calculations from basic principles highlight potential benefits of producing foods, but not fuels, from electro-microbial production of biomass.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"12 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857452","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}
Laura Luebbert, Delaney K. Sullivan, Maria Carilli, Kristján Eldjárn Hjörleifsson, Alexander Viloria Winnett, Tara Chari, Lior Pachter
{"title":"Detection of viral sequences at single-cell resolution identifies novel viruses associated with host gene expression changes","authors":"Laura Luebbert, Delaney K. Sullivan, Maria Carilli, Kristján Eldjárn Hjörleifsson, Alexander Viloria Winnett, Tara Chari, Lior Pachter","doi":"10.1038/s41587-025-02614-y","DOIUrl":"https://doi.org/10.1038/s41587-025-02614-y","url":null,"abstract":"<p>The increasing use of high-throughput sequencing methods in research, agriculture and healthcare provides an opportunity for the cost-effective surveillance of viral diversity and investigation of virus–disease correlation. However, existing methods for identifying viruses in sequencing data rely on and are limited to reference genomes or cannot retain single-cell resolution through cell barcode tracking. We introduce a method that accurately and rapidly detects viral sequences in bulk and single-cell transcriptomics data based on the highly conserved RdRP protein, enabling the detection of over 100,000 RNA virus species. The analysis of viral presence and host gene expression in parallel at single-cell resolution allows for the characterization of host viromes and the identification of viral tropism and host responses. We apply our method to peripheral blood mononuclear cell data from rhesus macaques with Ebola virus disease and describe previously unknown putative viruses. Moreover, we are able to accurately predict viral presence in individual cells based on macaque gene expression.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"50 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857453","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}
Jiacheng Hu, Mengyue Guo, Qiang Gao, He Jia, Mingyang He, Zhiwei Wang, Lina Guo, Guanwen Liu, Quan Gao, Kevin Tianmeng Zhao
{"title":"QBEmax is a sequence-permuted and internally protected base editor","authors":"Jiacheng Hu, Mengyue Guo, Qiang Gao, He Jia, Mingyang He, Zhiwei Wang, Lina Guo, Guanwen Liu, Quan Gao, Kevin Tianmeng Zhao","doi":"10.1038/s41587-025-02641-9","DOIUrl":"https://doi.org/10.1038/s41587-025-02641-9","url":null,"abstract":"<p>Cytosine base editors (CBEs) show promise for multiplex gene knockout applications, but impure edits, indels and off-targets still frequently occur. We describe here QBEmax, which exhibits high efficiency, low indel and off-targets and high product purity with up to 99.8% of edits comprised of C-to-T. Through molecular dynamic modeling, QBEmax presents as a compact and stable base editor that shields protected bases from undesired repair processes.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"17 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853219","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}
Michelle S. Frei, Samantha A. Sanchez, Xinchang He, Longwei Liu, Falk Schneider, Zichen Wang, Hiroyuki Hakozaki, Yajuan Li, Anne C. Lyons, Theresa V. Rohm, Jerrold M. Olefsky, Lingyan Shi, Johannes Schöneberg, Scott E. Fraser, Sohum Mehta, Yingxiao Wang, Jin Zhang
{"title":"Far-red chemigenetic kinase biosensors enable multiplexed and super-resolved imaging of signaling networks","authors":"Michelle S. Frei, Samantha A. Sanchez, Xinchang He, Longwei Liu, Falk Schneider, Zichen Wang, Hiroyuki Hakozaki, Yajuan Li, Anne C. Lyons, Theresa V. Rohm, Jerrold M. Olefsky, Lingyan Shi, Johannes Schöneberg, Scott E. Fraser, Sohum Mehta, Yingxiao Wang, Jin Zhang","doi":"10.1038/s41587-025-02642-8","DOIUrl":"https://doi.org/10.1038/s41587-025-02642-8","url":null,"abstract":"<p>Fluorescent biosensors have advanced biomedical research by enabling direct live-cell measurements of signaling activities. However, current technology offers limited resolution and dimensionality, impeding our ability to resolve and interrogate spatiotemporally regulated networks of signaling activities. Here we introduce highly sensitive chemigenetic kinase activity biosensors that combine the genetically encodable self-labeling tag, HaloTag7, with far-red-emitting synthetic fluorophores. This technology enables both four-dimensional activity imaging and functional super-resolution imaging using stimulated emission depletion and other high-resolution microscopy techniques, permitting signaling activity to be detected across scales with the necessary resolution. Stimulated emission depletion imaging enabled the investigation of protein kinase A activity at individual clathrin-coated pits. We further demonstrate imaging of up to five analytes in single living cells, an increase in the dimensionality of biosensor multiplexing. Multiplexed imaging of cellular responses to the activation of different G-protein-coupled receptors (GPCRs) allowed quantitative measurements of spatiotemporal network states downstream of individual GPCR–ligand pairs.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"14 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853117","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}
{"title":"AI tool adjusts for ancestral bias in genetic data","authors":"Iris Marchal","doi":"10.1038/s41587-025-02651-7","DOIUrl":"https://doi.org/10.1038/s41587-025-02651-7","url":null,"abstract":"<p>Human ancestry has a considerable impact on gene expression, but genomic datasets for disease analysis severely underrepresent non-European populations, thereby limiting the advancement of precision medicine. In a paper in <i>Nature Communications</i>, Smith et al. introduce a machine learning tool to mitigate the effects of ancestral bias in transcriptomic data.</p><p>The tool, called PhyloFrame, creates ancestry-aware signatures of disease by integrating population genomics data with smaller, disease-relevant training datasets. PhyloFrame uses a logistic regression model with LASSO penalty to obtain an initial set of disease-relevant genes. It then uses population genomics data to help compensate for data distribution shifts caused by human ancestry differences. In short, PhyloFrame projects the initial disease signature onto a functional interaction network, extending the network to include the first and second neighbors of each signature gene. This new set is then filtered by a statistic defined as enhanced allele frequency (EAF) — which captures population-specific allelic enrichment in healthy tissue — to identify ancestrally diverse genes that interact with the original signature. From each ancestry, a selected subset of genes with high EAF and gene expression variability in the training data are added to the PhyloFrame signature. Retraining the model with the forced inclusion of these equitable genes results in a signature of disease that generalizes to all populations, even if not represented in the training data.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"7 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831851","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}
{"title":"People","authors":"","doi":"10.1038/s41587-025-02637-5","DOIUrl":"https://doi.org/10.1038/s41587-025-02637-5","url":null,"abstract":"Recent moves of note in and around the biotech and pharma industries.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"183 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831825","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}
{"title":"Not just obesity: GLP-1 receptor agonists advance on addiction","authors":"","doi":"10.1038/s41587-025-02644-6","DOIUrl":"https://doi.org/10.1038/s41587-025-02644-6","url":null,"abstract":"GLP-1 agonists may lessen alcohol, smoking and possibly drug addictions. Evidence from clinical trials remains sparse, but that is about to change.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"38 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831831","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}
{"title":"Spotlight on cancer immunotherapies","authors":"","doi":"10.1038/s41587-025-02645-5","DOIUrl":"https://doi.org/10.1038/s41587-025-02645-5","url":null,"abstract":"Advances in cancer immunotherapy have shown promising results for treatment of tumors, yet challenges related to therapeutic efficacy and manufacturing processes need to be overcome.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"74 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831853","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}
{"title":"Turn cold tumors hot by reprogramming the tumor microenvironment","authors":"Xiangliang Yuan, Yi Xiao, Dihua Yu","doi":"10.1038/s41587-025-02597-w","DOIUrl":"https://doi.org/10.1038/s41587-025-02597-w","url":null,"abstract":"The identification of novel targets together with technological advances is transforming our ability to effectively modulate the tumor microenvironment.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"40 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831524","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}