Cell systems最新文献_第5页

Deciphering protein mutation-phenotype linkages from CRISPR-based tiling mutagenesis screens. 从基于crispr的平铺诱变筛选中解读蛋白质突变-表型联系。

IF 7.7

Cell systems Pub Date : 2026-08-19 Epub Date: 2026-06-26 DOI: 10.1016/j.cels.2026.101651

Wei He, Jen-Wei Huang, Yalong Wang, Samuel B Hayward, Giuseppe Leuzzi, Rongjie Fu, Shuyue Wang, Alina Vaitsiankova, Yiwen Chen, Mark T Bedford, Raphael Guerois, Alberto Ciccia, Han Xu

{"title":"Deciphering protein mutation-phenotype linkages from CRISPR-based tiling mutagenesis screens.","authors":"Wei He, Jen-Wei Huang, Yalong Wang, Samuel B Hayward, Giuseppe Leuzzi, Rongjie Fu, Shuyue Wang, Alina Vaitsiankova, Yiwen Chen, Mark T Bedford, Raphael Guerois, Alberto Ciccia, Han Xu","doi":"10.1016/j.cels.2026.101651","DOIUrl":"10.1016/j.cels.2026.101651","url":null,"abstract":"CRISPR-based high-throughput mutagenesis screens enable systematic mapping of mutations to phenotypes, yet deciphering mutation-phenotype links remains challenging. Here, we present ProTiler-Mut, a versatile computational framework that leverages tiling mutagenesis screens, which introduce variants across entire protein sequences, to analyze mutation effects at the levels of residues, substructures, and protein-protein interactions (PPIs). Applying ProTiler-Mut to multi-condition base-editing (BE) screens targeting DNA damage response proteins and T cell regulators, we define a separation-of-function (SoF) category beyond the conventional loss-of-function (LoF) and gain-of-function (GoF) classes, where SoF mutations show the strongest enrichment for ClinVar-annotated pathogenic variants. ProTiler-Mut also identifies candidate substructures that enable functional inference of unscreened pathogenic mutations and prioritizes candidate phenotype-associated PPIs potentially disrupted by functional variants. Using ProTiler-Mut, in cells with elevated programmed cell death 1 (PD-1) expression, we identify pathogenic GoF mutations that constitute a substructure that may disrupt mitogen-activated protein kinase (MAPK)1-RSK1 interactions and lead to MAPK activation. Finally, we show that ProTiler-Mut is applicable across different mutagenesis screening platforms. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101651"},"PeriodicalIF":7.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148341426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The emergence of the fractal bronchial tree. 分形支气管树的出现。

IF 7.7

Cell systems Pub Date : 2026-08-19 Epub Date: 2026-08-13 DOI: 10.1016/j.cels.2026.101704

Malte Mederacke, Kevin A Yamauchi, Nikolaos Doumpas, Laura Schaumann, Jonathan Sperl, Thomas Weikert, D Merrill Dane, Connie C W Hsia, Maurice Pradella, Jens Bremerich, Roman Vetter, Dagmar Iber

引用次数: 0

Mechanical feedback drives fractal airway organization. 机械反馈驱动分形气道组织。

IF 7.7

Cell systems Pub Date : 2026-08-19 DOI: 10.1016/j.cels.2026.101705

Maijia Liao

引用次数: 0

High-throughput DNA engineering by mating bacteria. 通过交配细菌进行高通量DNA工程。

IF 7.7

Cell systems Pub Date : 2026-08-19 Epub Date: 2026-07-01 DOI: 10.1016/j.cels.2026.101656

Takeshi Matsui, Po-Hsiang Hung, Han Mei, Xianan Liu, Fangfei Li, John Collins, Weiyi Li, Darach Miller, Neil Wilson, Esteban Toro, Geoffrey J Taghon, Gavin Sherlock, Sasha Levy

{"title":"High-throughput DNA engineering by mating bacteria.","authors":"Takeshi Matsui, Po-Hsiang Hung, Han Mei, Xianan Liu, Fangfei Li, John Collins, Weiyi Li, Darach Miller, Neil Wilson, Esteban Toro, Geoffrey J Taghon, Gavin Sherlock, Sasha Levy","doi":"10.1016/j.cels.2026.101656","DOIUrl":"10.1016/j.cels.2026.101656","url":null,"abstract":"We introduce SCRIVENER (sequential conjugation and recombination for in vivo elongation of nucleotides with low errors), an in vivo DNA assembly platform that streamlines and scales DNA engineering. SCRIVENER combines bacterial conjugation, in vivo DNA cutting, and homologous recombination to stitch DNA blocks together by mating E. coli in large arrays or pools. This approach is simpler, cheaper, and higher throughput than methods requiring DNA to be moved in and out of cells. We performed over 5,000 assemblies with 2 to 19 blocks (240 bp-12 kb) and assembled constructs up to 81 kb with high fidelity. Most errors are deletions between long repeats, but SCRIVENER minimizes their impact by enabling high-replication assembly and sequence verification at a nominal additional cost per replicate. The platform enables combinatorial library construction and DNA block reuse without PCR and is therefore a powerful tool to accelerate DNA design-build-test-learn cycles. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101656"},"PeriodicalIF":7.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Beyond differential expression: Differential variability as an underappreciated axis in transcriptomics. 超越差异表达：转录组学中未被充分认识的差异变异性。

IF 7.7

Cell systems Pub Date : 2026-08-19 DOI: 10.1016/j.cels.2026.101706

Chenxin Flora Jiang, Changhu Wang, Jingyi Jessica Li

引用次数: 0

Discovering what is possible: How synthetic biology illuminates development. 发现什么是可能的：合成生物学如何照亮发展。

IF 7.7

Cell systems Pub Date : 2026-08-19 Epub Date: 2026-06-04 DOI: 10.1016/j.cels.2026.101619

Nicholas T Hutchins, Alexandra Cao, Pulin Li

引用次数: 0

Integrated control of redox and energy metabolism by the membrane-bound and soluble transhydrogenases of Pseudomonas putida across metabolic regimes. 恶臭假单胞菌的膜结合和可溶性转氢酶对氧化还原和能量代谢的综合控制。

IF 7.7

Cell systems Pub Date : 2026-08-19 Epub Date: 2026-06-23 DOI: 10.1016/j.cels.2026.101646

Michele Partipilo, Giusi Favoino, Òscar Puiggené, Catarina Rocha, Carina Meiners, Nicolás Gurdo, Stefano Donati, Daniel C Volke, Pablo I Nikel

{"title":"Integrated control of redox and energy metabolism by the membrane-bound and soluble transhydrogenases of Pseudomonas putida across metabolic regimes.","authors":"Michele Partipilo, Giusi Favoino, Òscar Puiggené, Catarina Rocha, Carina Meiners, Nicolás Gurdo, Stefano Donati, Daniel C Volke, Pablo I Nikel","doi":"10.1016/j.cels.2026.101646","DOIUrl":"10.1016/j.cels.2026.101646","url":null,"abstract":"Redox homeostasis underpins microbial physiology and stress adaptation, yet the extent to which transhydrogenases contribute to these processes remains largely unexplored in most organisms. In this study, we reveal how Pseudomonas putida integrates two distinct transhydrogenases (membrane-bound PntAB and soluble SthA) into a flexible and reversible redox-balancing system supporting metabolic robustness across diverse conditions. Single deletions of either enzyme had minimal fitness impacts, whereas the double-mutant ΔpntAB ΔsthA exhibited growth defects, disrupted energy charge, and redox imbalance. Specifically, SthA proved essential for growth on acetate via a transcriptional regulator linked to glyoxylate metabolism. Notably, the activity of both transhydrogenases enabled cellular tolerance to formate by channeling the reducing equivalents released from the one-carbon (C1)-compound oxidation toward NAD⁺ regeneration. These findings delineate transhydrogenases as dynamic regulators of redox metabolism and energy conservation. Furthermore, this work positions P. putida as a prime host for redox-intensive applications and informs design principles for C1-based metabolic engineering. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101646"},"PeriodicalIF":7.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148310883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Living bacterial reservoir computers for information processing and sensing. 用于信息处理和感知的活细菌库计算机。

IF 7.7

Cell systems Pub Date : 2026-08-19 Epub Date: 2026-07-01 DOI: 10.1016/j.cels.2026.101654

Paul Ahavi, Thi-Ngoc-An Hoang, Philippe Meyer, Sylvie Berthier, Federica Fiorini, Florence Castelli, Olivier Epaulard, Audrey Le Gouellec, Jean-Loup Faulon

{"title":"Living bacterial reservoir computers for information processing and sensing.","authors":"Paul Ahavi, Thi-Ngoc-An Hoang, Philippe Meyer, Sylvie Berthier, Federica Fiorini, Florence Castelli, Olivier Epaulard, Audrey Le Gouellec, Jean-Loup Faulon","doi":"10.1016/j.cels.2026.101654","DOIUrl":"10.1016/j.cels.2026.101654","url":null,"abstract":"We introduce a systems-level approach to sensing and computing in which Escherichia coli acts as a living reservoir computer, performing complex information processing through its native growth responses without requiring genetic modification or specialized instrumentation. We validate this framework by accurately classifying early-stage COVID-19 plasma samples according to subsequent disease severity using only bacterial growth data, highlighting its prognostic potential without the need for infrastructure-dependent methods. By controlling nutrient media compositions, we also demonstrate that E. coli growth encodes nonlinear transformations that outperform linear regression, support vector machines, and multilayer perceptrons across diverse regression and classification tasks. More broadly, simulations across genome-scale metabolic models from multiple bacterial species support a link between phenotypic diversity and computational capacity. These findings position biological reservoir computing as a robust, scalable, and low-cost platform for intelligent biosensing, diagnostics, and hybrid bio-digital computation, while providing new mechanistic insights into the computational capabilities of living systems.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101654"},"PeriodicalIF":7.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted genomic editing of human gut Bacteroides species based on CRISPR-associated transposases. 基于crispr相关转座酶的人类肠道拟杆菌的靶向基因组编辑。

IF 7.7

Cell systems Pub Date : 2026-08-19 Epub Date: 2026-06-29 DOI: 10.1016/j.cels.2026.101650

Yucan Hu, Qingmei Li, Yingying Li, Yu Zeng, Linggang Zheng, Juntao Shen, Xiang Gao, Guo-Ping Zhao, Wei Zhao, Lei Dai

{"title":"Targeted genomic editing of human gut Bacteroides species based on CRISPR-associated transposases.","authors":"Yucan Hu, Qingmei Li, Yingying Li, Yu Zeng, Linggang Zheng, Juntao Shen, Xiang Gao, Guo-Ping Zhao, Wei Zhao, Lei Dai","doi":"10.1016/j.cels.2026.101650","DOIUrl":"10.1016/j.cels.2026.101650","url":null,"abstract":"Gut Bacteroides are abundant and critical to human health, yet most are genetically cumbersome, non-model microbes. A widely applicable editing tool for Bacteroides is essential for gut microbiome manipulation. Here, we develop STIB (ShCAST-based transient insertion system for Bacteroides), an efficient genome-editing tool derived from CRISPR-associated transposases that enables rapid and site-specific insertions independent of homologous recombination. By fusing a nicking homing endonuclease to the transposase and an ATPase to Cas12k, we systematically optimize STIB to minimize plasmid cointegration and achieve >97% on-target insertion. STIB exhibits broad applicability across different genomic loci in diverse Bacteroides species, including non-model species. Finally, we apply STIB to achieve species- and site-specific editing of distinct Bacteroides species within a complex synthetic gut microbiota. Overall, STIB expands the toolbox for the functional investigation and engineering of the human microbiome. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101650"},"PeriodicalIF":7.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Scalable enumeration and sampling of minimal metabolic pathways for organisms and communities. 生物体和群落的最小代谢途径的可扩展枚举和采样。

IF 7.7

Cell systems Pub Date : 2026-08-19 Epub Date: 2026-06-29 DOI: 10.1016/j.cels.2026.101653

Ove Øyås, Axel Theorell, Jörg Stelling

{"title":"Scalable enumeration and sampling of minimal metabolic pathways for organisms and communities.","authors":"Ove Øyås, Axel Theorell, Jörg Stelling","doi":"10.1016/j.cels.2026.101653","DOIUrl":"10.1016/j.cels.2026.101653","url":null,"abstract":"Many interactions in microbial consortia or tissues of multicellular organisms rely on networks of metabolite exchanges. To predict community function and composition beyond statistical correlations, one can use genome-scale metabolic models. However, comprehensive model analysis via metabolic pathways is a major challenge because pathway counts grow combinatorially with model size. Here, we define minimal pathways that yield compact representations of metabolic network capabilities. They generalize existing pathway concepts by allowing inhomogeneous constraints and targeted analysis of subnetworks, and we show how to enumerate and sample them efficiently via iterative minimization and pathway graphs. This enables applications such as assessing quantitative gene essentiality in the central metabolism of Escherichia coli, predicting metabolite exchanges associated with homeostasis and health in a host-microbe model of the human gut, and designing butyrate-producing microbial communities. Minimal pathways enable scalable analysis of metabolic subnetworks such as metabolite exchanges in uni- and multicellular systems. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101653"},"PeriodicalIF":7.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0