Cell systems最新文献_第7页

AlphaFold2 enables accurate deorphanization of ligands to single-pass receptors. AlphaFold2 可对单通道受体的配体进行精确的非形态化。

Cell systems Pub Date : 2024-11-20 Epub Date: 2024-11-13 DOI: 10.1016/j.cels.2024.10.004

Niels Banhos Danneskiold-Samsøe, Deniz Kavi, Kevin M Jude, Silas Boye Nissen, Lianna W Wat, Laetitia Coassolo, Meng Zhao, Galia Asae Santana-Oikawa, Beatrice Blythe Broido, K Christopher Garcia, Katrin J Svensson

{"title":"AlphaFold2 enables accurate deorphanization of ligands to single-pass receptors.","authors":"Niels Banhos Danneskiold-Samsøe, Deniz Kavi, Kevin M Jude, Silas Boye Nissen, Lianna W Wat, Laetitia Coassolo, Meng Zhao, Galia Asae Santana-Oikawa, Beatrice Blythe Broido, K Christopher Garcia, Katrin J Svensson","doi":"10.1016/j.cels.2024.10.004","DOIUrl":"10.1016/j.cels.2024.10.004","url":null,"abstract":"Secreted proteins play crucial roles in paracrine and endocrine signaling; however, identifying ligand-receptor interactions remains challenging. Here, we benchmarked AlphaFold2 (AF2) as a screening approach to identify extracellular ligands to single-pass transmembrane receptors. Key to the approach is the optimization of AF2 input and output for screening ligands against receptors to predict the most probable ligand-receptor interactions. The predictions were performed on ligand-receptor pairs not used for AF2 training. We demonstrate high discriminatory power and a success rate of close to 90% for known ligand-receptor pairs and 50% for a diverse set of experimentally validated interactions. Further, we show that screen accuracy does not correlate linearly with prediction of ligand-receptor interaction. These results demonstrate a proof of concept of a rapid and accurate screening platform to predict high-confidence cell-surface receptors for a diverse set of ligands by structural binding prediction, with potentially wide applicability for the understanding of cell-cell communication.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1046-1060.e3"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634554","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

Spatiotemporal dynamics during niche remodeling by super-colonizing microbiota in the mammalian gut. 哺乳动物肠道中超级定殖微生物群重塑生态位过程中的时空动态。

Cell systems Pub Date : 2024-11-20 Epub Date: 2024-11-13 DOI: 10.1016/j.cels.2024.10.007

Guillaume Urtecho, Thomas Moody, Yiming Huang, Ravi U Sheth, Miles Richardson, Hélène C Descamps, Andrew Kaufman, Opeyemi Lekan, Zetian Zhang, Florencia Velez-Cortes, Yiming Qu, Lucas Cohen, Deirdre Ricaurte, Travis E Gibson, Georg K Gerber, Christoph A Thaiss, Harris H Wang

{"title":"Spatiotemporal dynamics during niche remodeling by super-colonizing microbiota in the mammalian gut.","authors":"Guillaume Urtecho, Thomas Moody, Yiming Huang, Ravi U Sheth, Miles Richardson, Hélène C Descamps, Andrew Kaufman, Opeyemi Lekan, Zetian Zhang, Florencia Velez-Cortes, Yiming Qu, Lucas Cohen, Deirdre Ricaurte, Travis E Gibson, Georg K Gerber, Christoph A Thaiss, Harris H Wang","doi":"10.1016/j.cels.2024.10.007","DOIUrl":"10.1016/j.cels.2024.10.007","url":null,"abstract":"While fecal microbiota transplantation (FMT) has been shown to be effective in reversing gut dysbiosis, we lack an understanding of the fundamental processes underlying microbial engraftment in the mammalian gut. Here, we explored a murine gut colonization model leveraging natural inter-individual variations in gut microbiomes to elucidate the spatiotemporal dynamics of FMT. We identified a natural \"super-donor\" consortium that robustly engrafts into diverse recipients and resists reciprocal colonization. Temporal profiling of the gut microbiome showed an ordered succession of rapid engraftment by early colonizers within 72 h, followed by a slower emergence of late colonizers over 15-30 days. Moreover, engraftment was localized to distinct compartments of the gastrointestinal tract in a species-specific manner. Spatial metagenomic characterization suggested engraftment was mediated by simultaneous transfer of spatially co-localizing species from the super-donor consortia. These results offer a mechanism of super-donor colonization by which nutritional niches are expanded in a spatiotemporally dependent manner. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1002-1017.e4"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634556","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

Evaluation of Choudhary et al.: Single-cell gene expression dynamics in the E. coli oxidative stress response network. 对 Choudhary 等人的评价：大肠杆菌氧化应激反应网络中的单细胞基因表达动态

Cell systems Pub Date : 2024-11-20 DOI: 10.1016/j.cels.2024.10.011

Razan N Alnahhas, Mary J Dunlop

引用次数: 0

How do you anticipate computational protein design will change biotechnology and therapeutic development? 您预计计算蛋白质设计将如何改变生物技术和疗法开发？

Cell systems Pub Date : 2024-11-20 DOI: 10.1016/j.cels.2024.10.012

Derek N Woolfson, Lucy J Colwell, Zibo Chen, Anastassia A Vorobieva, Nicholas F Polizzi, Amelie Stein, Haiyan Liu, Fabio Parmeggiani, Anna Peacock, Rohit Singh, Neil King, Marinka Zitnik, Roberto A Chica

引用次数: 0

Plausible, robust biological oscillations through allelic buffering. 通过等位基因缓冲实现可信、稳健的生物振荡。

Cell systems Pub Date : 2024-11-20 Epub Date: 2024-11-05 DOI: 10.1016/j.cels.2024.10.002

Feng-Shu Hsieh, Duy P M Nguyen, Mathias S Heltberg, Chia-Chou Wu, Yi-Chen Lee, Mogens H Jensen, Sheng-Hong Chen

{"title":"Plausible, robust biological oscillations through allelic buffering.","authors":"Feng-Shu Hsieh, Duy P M Nguyen, Mathias S Heltberg, Chia-Chou Wu, Yi-Chen Lee, Mogens H Jensen, Sheng-Hong Chen","doi":"10.1016/j.cels.2024.10.002","DOIUrl":"10.1016/j.cels.2024.10.002","url":null,"abstract":"Biological oscillators can specify time- and dose-dependent functions via dedicated control of their oscillatory dynamics. However, how biological oscillators, which recurrently activate noisy biochemical processes, achieve robust oscillations remains unclear. Here, we characterize the long-term oscillations of p53 and its negative feedback regulator Mdm2 in single cells after DNA damage. Whereas p53 oscillates regularly, Mdm2 from a single MDM2 allele exhibits random unresponsiveness to ∼9% of p53 pulses. Using allelic-specific imaging of MDM2 activity, we show that MDM2 alleles buffer each other to maintain p53 pulse amplitude. Removal of MDM2 allelic buffering cripples the robustness of p53 amplitude, thereby elevating p21 levels and cell-cycle arrest. In silico simulations support that allelic buffering enhances the robustness of biological oscillators and broadens their plausible biochemical space. Our findings show how allelic buffering ensures robust p53 oscillations, highlighting the potential importance of allelic buffering for the emergence of robust biological oscillators during evolution. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1018-1032.e12"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592419","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

Putting proteins in context. 将蛋白质置于背景中。

Cell systems Pub Date : 2024-10-16 DOI: 10.1016/j.cels.2024.09.009

Mengzhou Hu, Trey Ideker

引用次数: 0

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":"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.","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":"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 (REPACRISPR) for conditional endogenous transcriptional regulation of genes in vitro and in vivo. Two REPACRISPR variants, REPACRISPRi and REPACRISPRa, 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 REPACRISPRa. We also established mathematical models to predict the dose-responsive transcriptional levels of a target endogenous gene controlled by REPACRISPRa. 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.","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

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

引用次数: 0