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Evolution in microbial microcosms is highly parallel, regardless of the presence of interacting species. 无论是否存在相互作用的物种,微生物微生态系统中的进化都是高度平行的。
Cell systems Pub Date : 2024-10-16 DOI: 10.1016/j.cels.2024.09.007
Nittay Meroz, Tal Livny, Gal Toledano, Yael Sorokin, Nesli Tovi, Jonathan Friedman
{"title":"Evolution in microbial microcosms is highly parallel, regardless of the presence of interacting species.","authors":"Nittay Meroz, Tal Livny, Gal Toledano, Yael Sorokin, Nesli Tovi, Jonathan Friedman","doi":"10.1016/j.cels.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.cels.2024.09.007","url":null,"abstract":"<p><p>Evolution often follows similar trajectories in replicate populations, suggesting that it may be predictable. However, populations are naturally embedded in multispecies communities, and the extent to which evolution is contingent on the specific species interacting with the focal population is still largely unexplored. Here, we study adaptations in strains of 11 different species, experimentally evolved both in isolation and in various pairwise co-cultures. Although partner-specific effects are detectable, evolution was mostly shared between strains evolved with different partners; similar changes occurred in strains' growth abilities, in community properties, and in about half of the repeatedly mutated genes. This pattern persisted even in species pre-adapted to the abiotic conditions. These findings indicate that evolution may not always depend strongly on the biotic environment, making predictions regarding coevolutionary dynamics less challenging than previously thought. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 10","pages":"930-940.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483083","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
A digital CRISPR-dCas9-based gene remodeling biocomputer programmed by dietary compounds in mammals. 基于 CRISPR-dCas9 的数字化基因重塑生物计算机,由哺乳动物体内的膳食化合物编程。
Cell systems Pub Date : 2024-10-16 Epub Date: 2024-10-09 DOI: 10.1016/j.cels.2024.09.002
Jianli Yin, Hang Wan, Deqiang Kong, Xingwan Liu, Ying Guan, Jiali Wu, Yang Zhou, Xiaoding Ma, Chunbo Lou, Haifeng Ye, Ningzi Guan
{"title":"A digital CRISPR-dCas9-based gene remodeling biocomputer programmed by dietary compounds in mammals.","authors":"Jianli Yin, Hang Wan, Deqiang Kong, Xingwan Liu, Ying Guan, Jiali Wu, Yang Zhou, Xiaoding Ma, Chunbo Lou, Haifeng Ye, Ningzi Guan","doi":"10.1016/j.cels.2024.09.002","DOIUrl":"10.1016/j.cels.2024.09.002","url":null,"abstract":"<p><p>CRISPR-dCas9 (dead Cas9 protein) technology, combined with chemical molecules and light-triggered genetic switches, offers customizable control over gene perturbation. However, these simple ON/OFF switches cannot precisely determine the sophisticated perturbation process. Here, we developed a resveratrol and protocatechuic acid-programmed CRISPR-mediated gene remodeling biocomputer (REPA<sub>CRISPR</sub>) for conditional endogenous transcriptional regulation of genes in vitro and in vivo. Two REPA<sub>CRISPR</sub> variants, REPA<sub>CRISPRi</sub> and REPA<sub>CRISPRa</sub>, were designed for the logic control of gene inhibition and activation, respectively. We successfully demonstrated the digital computations of single or multiplexed endogenous gene transcription by using REPA<sub>CRISPRa</sub>. We also established mathematical models to predict the dose-responsive transcriptional levels of a target endogenous gene controlled by REPA<sub>CRISPRa</sub>. Moreover, high levels of endogenous gene activation in mice mediated by the AND logic gate demonstrated computational control of CRISPR-dCas9-based epigenome remodeling in mice. This CRISPR-based biocomputer expands the synthetic biology toolbox and can potentially advance gene-based precision medicine. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"941-955.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395959","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
SpotGF: Denoising spatially resolved transcriptomics data using an optimal transport-based gene filtering algorithm. SpotGF:使用基于传输的最优基因过滤算法对空间解析转录组学数据进行去噪处理。
Cell systems Pub Date : 2024-10-16 Epub Date: 2024-10-07 DOI: 10.1016/j.cels.2024.09.005
Lin Du, Jingmin Kang, Yong Hou, Hai-Xi Sun, Bohan Zhang
{"title":"SpotGF: Denoising spatially resolved transcriptomics data using an optimal transport-based gene filtering algorithm.","authors":"Lin Du, Jingmin Kang, Yong Hou, Hai-Xi Sun, Bohan Zhang","doi":"10.1016/j.cels.2024.09.005","DOIUrl":"10.1016/j.cels.2024.09.005","url":null,"abstract":"<p><p>Spatially resolved transcriptomics (SRT) combines gene expression profiles with the physical locations of cells in their native states but suffers from unpredictable spatial noise due to cell damage during cryosectioning and exposure to reagents for staining and mRNA release. To address this noise, we developed SpotGF, an algorithm for denoising SRT data using optimal transport-based gene filtering. SpotGF quantifies diffusion patterns numerically, distinguishing widespread expression genes from aggregated expression genes and filtering out the former as noise. Unlike conventional denoising methods, SpotGF preserves raw sequencing data, thereby avoiding false positives that can arise from imputation. Additionally, SpotGF demonstrates superior performance in cell clustering, identifying potential marker genes, and annotating cell types. Overall, SpotGF has the potential to become a crucial preprocessing step in the downstream analysis of SRT data. The SpotGF software is freely available at GitHub. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"969-981.e6"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395961","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
Transcriptional memory formation: Battles between transcription factors and repressive chromatin. 转录记忆的形成:转录因子与抑制染色质之间的斗争
Cell systems Pub Date : 2024-10-16 DOI: 10.1016/j.cels.2024.09.008
Zuodong Zhao, Bing Zhu
{"title":"Transcriptional memory formation: Battles between transcription factors and repressive chromatin.","authors":"Zuodong Zhao, Bing Zhu","doi":"10.1016/j.cels.2024.09.008","DOIUrl":"https://doi.org/10.1016/j.cels.2024.09.008","url":null,"abstract":"<p><p>Transcriptional memory allows cells to respond to previously experienced signals in a faster, stronger, and more sensitive manner. Using synthetic biology approaches, Fan and colleagues uncovered the critical interplays between transcription factors and repressive chromatin in consolidating transcriptional memory.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 10","pages":"895-897"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483086","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
Automated single-cell omics end-to-end framework with data-driven batch inference. 采用数据驱动批量推理的自动化单细胞全息端到端框架。
Cell systems Pub Date : 2024-10-16 Epub Date: 2024-10-03 DOI: 10.1016/j.cels.2024.09.003
Yuan Wang, William Thistlethwaite, Alicja Tadych, Frederique Ruf-Zamojski, Daniel J Bernard, Antonio Cappuccio, Elena Zaslavsky, Xi Chen, Stuart C Sealfon, Olga G Troyanskaya
{"title":"Automated single-cell omics end-to-end framework with data-driven batch inference.","authors":"Yuan Wang, William Thistlethwaite, Alicja Tadych, Frederique Ruf-Zamojski, Daniel J Bernard, Antonio Cappuccio, Elena Zaslavsky, Xi Chen, Stuart C Sealfon, Olga G Troyanskaya","doi":"10.1016/j.cels.2024.09.003","DOIUrl":"10.1016/j.cels.2024.09.003","url":null,"abstract":"<p><p>To facilitate single-cell multi-omics analysis and improve reproducibility, we present single-cell pipeline for end-to-end data integration (SPEEDI), a fully automated end-to-end framework for batch inference, data integration, and cell-type labeling. SPEEDI introduces data-driven batch inference and transforms the often heterogeneous data matrices obtained from different samples into a uniformly annotated and integrated dataset. Without requiring user input, it automatically selects parameters and executes pre-processing, sample integration, and cell-type mapping. It can also perform downstream analyses of differential signals between treatment conditions and gene functional modules. SPEEDI's data-driven batch-inference method works with widely used integration and cell-typing tools. By developing data-driven batch inference, providing full end-to-end automation, and eliminating parameter selection, SPEEDI improves reproducibility and lowers the barrier to obtaining biological insight from these valuable single-cell datasets. The SPEEDI interactive web application can be accessed at https://speedi.princeton.edu/. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"982-990.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376460","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
Data-driven batch detection enhances single-cell omics data analysis. 数据驱动的批量检测增强了单细胞组学数据分析。
Cell systems Pub Date : 2024-10-16 DOI: 10.1016/j.cels.2024.09.011
Ziqi Zhang, Xiuwei Zhang
{"title":"Data-driven batch detection enhances single-cell omics data analysis.","authors":"Ziqi Zhang, Xiuwei Zhang","doi":"10.1016/j.cels.2024.09.011","DOIUrl":"https://doi.org/10.1016/j.cels.2024.09.011","url":null,"abstract":"<p><p>In single-cell omics studies, data are typically collected across multiple batches, resulting in batch effects: technical confounders that introduce noise and distort data distribution. Correcting these effects is challenging due to their unknown sources, nonlinear distortions, and the difficulty of accurately assigning data to batches that are optimal for integration methods.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 10","pages":"893-894"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483082","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
How can concepts from ecology enable insights about cellular communities? 生态学的概念如何帮助我们了解细胞群落?
Cell systems Pub Date : 2024-10-16 DOI: 10.1016/j.cels.2024.09.010
Anna Weiss, Matti Gralka, Karoline Faust, David Basanta Gutierrez, Kenneth Pienta, Xu Zhou, Ophelia S Venturelli, Sean Gibbons, Mo Ebrahimkhani, Nika Shakiba, Shaohua Ma
{"title":"How can concepts from ecology enable insights about cellular communities?","authors":"Anna Weiss, Matti Gralka, Karoline Faust, David Basanta Gutierrez, Kenneth Pienta, Xu Zhou, Ophelia S Venturelli, Sean Gibbons, Mo Ebrahimkhani, Nika Shakiba, Shaohua Ma","doi":"10.1016/j.cels.2024.09.010","DOIUrl":"10.1016/j.cels.2024.09.010","url":null,"abstract":"","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 10","pages":"885-890"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483084","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
Protein turnover regulation is critical for influenza A virus infection. 蛋白质周转调节对甲型流感病毒感染至关重要。
Cell systems Pub Date : 2024-10-16 Epub Date: 2024-10-04 DOI: 10.1016/j.cels.2024.09.004
Yiqi Huang, Christian Urban, Philipp Hubel, Alexey Stukalov, Andreas Pichlmair
{"title":"Protein turnover regulation is critical for influenza A virus infection.","authors":"Yiqi Huang, Christian Urban, Philipp Hubel, Alexey Stukalov, Andreas Pichlmair","doi":"10.1016/j.cels.2024.09.004","DOIUrl":"10.1016/j.cels.2024.09.004","url":null,"abstract":"<p><p>The abundance of a protein is defined by its continuous synthesis and degradation, a process known as protein turnover. Here, we systematically profiled the turnover of proteins in influenza A virus (IAV)-infected cells using a pulse-chase stable isotope labeling by amino acids in cell culture (SILAC)-based approach combined with downstream statistical modeling. We identified 1,798 virus-affected proteins with turnover changes (tVAPs) out of 7,739 detected proteins (data available at pulsechase.innatelab.org). In particular, the affected proteins were involved in RNA transcription, splicing and nuclear transport, protein translation and stability, and energy metabolism. Many tVAPs appeared to be known IAV-interacting proteins that regulate virus propagation, such as KPNA6, PPP6C, and POLR2A. Notably, our analysis identified additional IAV host and restriction factors, such as the splicing factor GPKOW, that exhibit significant turnover rate changes while their total abundance is minimally affected. Overall, we show that protein turnover is a critical factor both for virus replication and antiviral defense.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"911-929.e8"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378731","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
Entrainment and multi-stability of the p53 oscillator in human cells. 人体细胞中 p53 振荡器的协调性和多重稳定性。
Cell systems Pub Date : 2024-10-16 Epub Date: 2024-10-04 DOI: 10.1016/j.cels.2024.09.001
Alba Jiménez, Alessandra Lucchetti, Mathias S Heltberg, Liv Moretto, Carlos Sanchez, Ashwini Jambhekar, Mogens H Jensen, Galit Lahav
{"title":"Entrainment and multi-stability of the p53 oscillator in human cells.","authors":"Alba Jiménez, Alessandra Lucchetti, Mathias S Heltberg, Liv Moretto, Carlos Sanchez, Ashwini Jambhekar, Mogens H Jensen, Galit Lahav","doi":"10.1016/j.cels.2024.09.001","DOIUrl":"10.1016/j.cels.2024.09.001","url":null,"abstract":"<p><p>The tumor suppressor p53 responds to cellular stress and activates transcription programs critical for regulating cell fate. DNA damage triggers oscillations in p53 levels with a robust period. Guided by the theory of synchronization and entrainment, we developed a mathematical model and experimental system to test the ability of the p53 oscillator to entrain to external drug pulses of various periods and strengths. We found that the p53 oscillator can be locked and entrained to a wide range of entrainment modes. External periods far from p53's natural oscillations increased the heterogeneity between individual cells whereas stronger inputs reduced it. Single-cell measurements allowed deriving the phase response curves (PRCs) and multiple Arnold tongues of p53. In addition, multi-stability and non-linear behaviors were mathematically predicted and experimentally detected, including mode hopping, period doubling, and chaos. Our work revealed critical dynamical properties of the p53 oscillator and provided insights into understanding and controlling it. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"956-968.e3"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378730","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
Exploring "dark-matter" protein folds using deep learning. 利用深度学习探索 "暗物质 "蛋白质折叠。
Cell systems Pub Date : 2024-10-16 Epub Date: 2024-10-08 DOI: 10.1016/j.cels.2024.09.006
Zander Harteveld, Alexandra Van Hall-Beauvais, Irina Morozova, Joshua Southern, Casper Goverde, Sandrine Georgeon, Stéphane Rosset, Michëal Defferrard, Andreas Loukas, Pierre Vandergheynst, Michael M Bronstein, Bruno E Correia
{"title":"Exploring \"dark-matter\" protein folds using deep learning.","authors":"Zander Harteveld, Alexandra Van Hall-Beauvais, Irina Morozova, Joshua Southern, Casper Goverde, Sandrine Georgeon, Stéphane Rosset, Michëal Defferrard, Andreas Loukas, Pierre Vandergheynst, Michael M Bronstein, Bruno E Correia","doi":"10.1016/j.cels.2024.09.006","DOIUrl":"10.1016/j.cels.2024.09.006","url":null,"abstract":"<p><p>De novo protein design explores uncharted sequence and structure space to generate novel proteins not sampled by evolution. A main challenge in de novo design involves crafting \"designable\" structural templates to guide the sequence searches toward adopting target structures. We present a convolutional variational autoencoder that learns patterns of protein structure, dubbed Genesis. We coupled Genesis with trRosetta to design sequences for a set of protein folds and found that Genesis is capable of reconstructing native-like distance and angle distributions for five native folds and three novel, the so-called \"dark-matter\" folds as a demonstration of generalizability. We used a high-throughput assay to characterize the stability of the designs through protease resistance, obtaining encouraging success rates for folded proteins. Genesis enables exploration of the protein fold space within minutes, unrestricted by protein topologies. Our approach addresses the backbone designability problem, showing that small neural networks can efficiently learn structural patterns in proteins. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"898-910.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395960","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
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