Cell systems最新文献

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 : 2024-11-04 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","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

Markov field network model of multi-modal data predicts effects of immune system perturbations on intravenous BCG vaccination in macaques. 多模态数据的马尔可夫场网络模型可预测免疫系统扰动对猕猴静脉注射卡介苗的影响。

Cell systems Pub Date : 2024-10-29 DOI: 10.1016/j.cels.2024.10.001

Shu Wang, Amy J Myers, Edward B Irvine, Chuangqi Wang, Pauline Maiello, Mark A Rodgers, Jaime Tomko, Kara Kracinovsky, H Jacob Borish, Michael C Chao, Douaa Mugahid, Patricia A Darrah, Robert A Seder, Mario Roederer, Charles A Scanga, Philana Ling Lin, Galit Alter, Sarah M Fortune, JoAnne L Flynn, Douglas A Lauffenburger

{"title":"Markov field network model of multi-modal data predicts effects of immune system perturbations on intravenous BCG vaccination in macaques.","authors":"Shu Wang, Amy J Myers, Edward B Irvine, Chuangqi Wang, Pauline Maiello, Mark A Rodgers, Jaime Tomko, Kara Kracinovsky, H Jacob Borish, Michael C Chao, Douaa Mugahid, Patricia A Darrah, Robert A Seder, Mario Roederer, Charles A Scanga, Philana Ling Lin, Galit Alter, Sarah M Fortune, JoAnne L Flynn, Douglas A Lauffenburger","doi":"10.1016/j.cels.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.cels.2024.10.001","url":null,"abstract":"Analysis of multi-modal datasets can identify multi-scale interactions underlying biological systems but can be beset by spurious connections due to indirect impacts propagating through an unmapped biological network. For example, studies in macaques have shown that Bacillus Calmette-Guerin (BCG) vaccination by an intravenous route protects against tuberculosis, correlating with changes across various immune data modes. To eliminate spurious correlations and identify critical immune interactions in a public multi-modal dataset (systems serology, cytokines, and cytometry) of vaccinated macaques, we applied Markov fields (MFs), a data-driven approach that explains vaccine efficacy and immune correlations via multivariate network paths, without requiring large numbers of samples (i.e., macaques) relative to multivariate features. We find that integrating multiple data modes with MFs helps remove spurious connections. Finally, we used the MF to predict outcomes of perturbations at various immune nodes, including an experimentally validated B cell depletion that induced network-wide shifts without reducing vaccine protection.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592417","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

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":null,"pages":null},"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

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":"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.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":null,"pages":null},"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

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

引用次数: 0