Cell Systems最新文献_第6页

What do you most hope spatial molecular profiling will help us understand? Part 1. 你最希望空间分子图谱能帮助我们理解什么?第1部分。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-06-21 DOI: 10.1016/j.cels.2023.05.009

Fabian J Theis, Daniel Dar, Roser Vento-Tormo, Sanja Vicković, Linghua Wang, Luciane T Kagohara, André F Rendeiro, Johanna A Joyce

引用次数: 0

A vast evolutionarily transient translatome contributes to phenotype and fitness. 一个巨大的进化瞬时易位体对表型和适应性做出了贡献。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-05-17 Epub Date: 2023-05-09 DOI: 10.1016/j.cels.2023.04.002

Aaron Wacholder, Saurin Bipin Parikh, Nelson Castilho Coelho, Omer Acar, Carly Houghton, Lin Chou, Anne-Ruxandra Carvunis

{"title":"A vast evolutionarily transient translatome contributes to phenotype and fitness.","authors":"Aaron Wacholder, Saurin Bipin Parikh, Nelson Castilho Coelho, Omer Acar, Carly Houghton, Lin Chou, Anne-Ruxandra Carvunis","doi":"10.1016/j.cels.2023.04.002","DOIUrl":"10.1016/j.cels.2023.04.002","url":null,"abstract":"Translation is the process by which ribosomes synthesize proteins. Ribosome profiling recently revealed that many short sequences previously thought to be noncoding are pervasively translated. To identify protein-coding genes in this noncanonical translatome, we combine an integrative framework for extremely sensitive ribosome profiling analysis, iRibo, with high-powered selection inferences tailored for short sequences. We construct a reference translatome for Saccharomyces cerevisiae comprising 5,400 canonical and almost 19,000 noncanonical translated elements. Only 14 noncanonical elements were evolving under detectable purifying selection. A representative subset of translated elements lacking signatures of selection demonstrated involvement in processes including DNA repair, stress response, and post-transcriptional regulation. Our results suggest that most translated elements are not conserved protein-coding genes and contribute to genotype-phenotype relationships through fast-evolving molecular mechanisms.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 5","pages":"363-381.e8"},"PeriodicalIF":9.3,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9780394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reproducibility metrics for context-specific CRISPR screens. 特异性 CRISPR 筛选的再现性指标。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-05-17 DOI: 10.1016/j.cels.2023.04.003

Maximilian Billmann, Henry N Ward, Michael Aregger, Michael Costanzo, Brenda J Andrews, Charles Boone, Jason Moffat, Chad L Myers

{"title":"Reproducibility metrics for context-specific CRISPR screens.","authors":"Maximilian Billmann, Henry N Ward, Michael Aregger, Michael Costanzo, Brenda J Andrews, Charles Boone, Jason Moffat, Chad L Myers","doi":"10.1016/j.cels.2023.04.003","DOIUrl":"10.1016/j.cels.2023.04.003","url":null,"abstract":"CRISPR screens are used extensively to systematically interrogate the phenotype-to-genotype problem. In contrast to early CRISPR screens, which defined core cell fitness genes, most current efforts now aim to identify context-specific phenotypes that differentiate a cell line, genetic background, or condition of interest, such as a drug treatment. While CRISPR-related technologies have shown great promise and a fast pace of innovation, a better understanding of standards and methods for quality assessment of CRISPR screen results is crucial to guide technology development and application. Specifically, many commonly used metrics for quantifying screen quality do not accurately measure the reproducibility of context-specific hits. We highlight the importance of reporting reproducibility statistics that directly relate to the purpose of the screen and suggest the use of metrics that are sensitive to context-specific signal. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 5","pages":"418-422.e2"},"PeriodicalIF":9.3,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9630120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic interactions under the microscope. 显微镜下的基因相互作用。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-05-17 DOI: 10.1016/j.cels.2023.04.005

Colm J Ryan

引用次数: 0

Between noise and function: Toward a taxonomy of the non-canonical translatome. 在噪音与功能之间:走向非规范翻译组的分类。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-05-17 DOI: 10.1016/j.cels.2023.04.004

Zachary Ardern, Md Hassan Uz-Zaman

引用次数: 0

Parallel engineering and activity profiling of a base editor system. 基编辑器系统的并行工程和活动分析。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-05-17 DOI: 10.1016/j.cels.2023.03.007

John H C Fong, Hoi Yee Chu, Peng Zhou, Alan S L Wong

{"title":"Parallel engineering and activity profiling of a base editor system.","authors":"John H C Fong, Hoi Yee Chu, Peng Zhou, Alan S L Wong","doi":"10.1016/j.cels.2023.03.007","DOIUrl":"https://doi.org/10.1016/j.cels.2023.03.007","url":null,"abstract":"Selecting the most suitable existing base editors and engineering new variants for installing specific base conversions with maximal efficiency and minimal undesired edits are pivotal for precise genome editing applications. Here, we present a platform for creating and analyzing a library of engineered base editor variants to enable head-to-head evaluation of their editing performance at scale. Our comprehensive comparison provides quantitative measures on each variant's editing efficiency, purity, motif preference, and bias in generating single and multiple base conversions, while uncovering undesired higher indel generation rate and noncanonical base conversion for some of the existing base editors. In addition to engineering the base editor protein, we further applied this platform to investigate a hitherto underexplored engineering route and created guide RNA scaffold variants that augment the editor's base-editing activity. With the unknown performance and compatibility of the growing number of engineered parts including deaminase, CRISPR-Cas enzyme, and guide RNA scaffold variants for assembling the expanding collection of base editor systems, our platform addresses the unmet need for an unbiased, scalable method to benchmark their editing outcomes and accelerate the engineering of next-generation precise genome editors.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 5","pages":"392-403.e4"},"PeriodicalIF":9.3,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9597856","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}

引用次数: 1

Deciphering tumor ecosystems at super resolution from spatial transcriptomics with TESLA. 利用 TESLA 从空间转录组学的超分辨率解密肿瘤生态系统。

IF 9 1区生物学

Cell Systems Pub Date : 2023-05-17 Epub Date: 2023-05-09 DOI: 10.1016/j.cels.2023.03.008

Jian Hu, Kyle Coleman, Daiwei Zhang, Edward B Lee, Humam Kadara, Linghua Wang, Mingyao Li

{"title":"Deciphering tumor ecosystems at super resolution from spatial transcriptomics with TESLA.","authors":"Jian Hu, Kyle Coleman, Daiwei Zhang, Edward B Lee, Humam Kadara, Linghua Wang, Mingyao Li","doi":"10.1016/j.cels.2023.03.008","DOIUrl":"10.1016/j.cels.2023.03.008","url":null,"abstract":"Cell populations in the tumor microenvironment (TME), including their abundance, composition, and spatial location, are critical determinants of patient response to therapy. Recent advances in spatial transcriptomics (ST) have enabled the comprehensive characterization of gene expression in the TME. However, popular ST platforms, such as Visium, only measure expression in low-resolution spots and have large tissue areas that are not covered by any spots, which limits their usefulness in studying the detailed structure of TME. Here, we present TESLA, a machine learning framework for tissue annotation with pixel-level resolution in ST. TESLA integrates histological information with gene expression to annotate heterogeneous immune and tumor cells directly on the histology image. TESLA further detects unique TME features such as tertiary lymphoid structures, which represents a promising avenue for understanding the spatial architecture of the TME. Although we mainly illustrated the applications in cancer, TESLA can also be applied to other diseases.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 5","pages":"404-417.e4"},"PeriodicalIF":9.0,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2f/f4/nihms-1901443.PMC10246692.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9597858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A global genetic interaction network by single-cell imaging and machine learning. 单细胞成像和机器学习的全球遗传相互作用网络。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-05-17 DOI: 10.1016/j.cels.2023.03.003

Florian Heigwer, Christian Scheeder, Josephine Bageritz, Schayan Yousefian, Benedikt Rauscher, Christina Laufer, Sergi Beneyto-Calabuig, Maja Christina Funk, Vera Peters, Maria Boulougouri, Jana Bilanovic, Thilo Miersch, Barbara Schmitt, Claudia Blass, Fillip Port, Michael Boutros

{"title":"A global genetic interaction network by single-cell imaging and machine learning.","authors":"Florian Heigwer, Christian Scheeder, Josephine Bageritz, Schayan Yousefian, Benedikt Rauscher, Christina Laufer, Sergi Beneyto-Calabuig, Maja Christina Funk, Vera Peters, Maria Boulougouri, Jana Bilanovic, Thilo Miersch, Barbara Schmitt, Claudia Blass, Fillip Port, Michael Boutros","doi":"10.1016/j.cels.2023.03.003","DOIUrl":"https://doi.org/10.1016/j.cels.2023.03.003","url":null,"abstract":"Cellular and organismal phenotypes are controlled by complex gene regulatory networks. However, reference maps of gene function are still scarce across different organisms. Here, we generated synthetic genetic interaction and cell morphology profiles of more than 6,800 genes in cultured Drosophila cells. The resulting map of genetic interactions was used for machine learning-based gene function discovery, assigning functions to genes in 47 modules. Furthermore, we devised Cytoclass as a method to dissect genetic interactions for discrete cell states at the single-cell resolution. This approach identified an interaction of Cdk2 and the Cop9 signalosome complex, triggering senescence-associated secretory phenotypes and immunogenic conversion in hemocytic cells. Together, our data constitute a genome-scale resource of functional gene profiles to uncover the mechanisms underlying genetic interactions and their plasticity at the single-cell level.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 5","pages":"346-362.e6"},"PeriodicalIF":9.3,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9949339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Coupled oscillator cooperativity as a control mechanism in chronobiology. 耦合振荡器协同性在时间生物学中的控制机制。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-05-17 DOI: 10.1016/j.cels.2023.04.001

Mathias S Heltberg, Yuanxu Jiang, Yingying Fan, Zhibo Zhang, Malthe S Nordentoft, Wei Lin, Long Qian, Qi Ouyang, Mogens H Jensen, Ping Wei

{"title":"Coupled oscillator cooperativity as a control mechanism in chronobiology.","authors":"Mathias S Heltberg, Yuanxu Jiang, Yingying Fan, Zhibo Zhang, Malthe S Nordentoft, Wei Lin, Long Qian, Qi Ouyang, Mogens H Jensen, Ping Wei","doi":"10.1016/j.cels.2023.04.001","DOIUrl":"https://doi.org/10.1016/j.cels.2023.04.001","url":null,"abstract":"Control of dynamical processes is vital for maintaining correct cell regulation and cell-fate decisions. Numerous regulatory networks show oscillatory behavior; however, our knowledge of how one oscillator behaves when stimulated by two or more external oscillatory signals is still missing. We explore this problem by constructing a synthetic oscillatory system in yeast and stimulate it with two external oscillatory signals. Letting model verification and prediction operate in a tight interplay with experimental observations, we find that stimulation with two external signals expands the plateau of entrainment and reduces the fluctuations of oscillations. Furthermore, by adjusting the phase differences of external signals, one can control the amplitude of oscillations, which is understood through the signal delay of the unperturbed oscillatory network. With this we reveal a direct amplitude dependency of downstream gene transcription. Taken together, these results suggest a new path to control oscillatory systems by coupled oscillator cooperativity.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 5","pages":"382-391.e5"},"PeriodicalIF":9.3,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9966248","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}

引用次数: 1

Emerging questions in transcriptional regulation. 转录调控中的新问题。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-04-19 DOI: 10.1016/j.cels.2023.03.005

Elphège P Nora, Stein Aerts, Patricia J Wittkopp, Harmen J Bussemaker, Martha Bulyk, Saurabh Sinha, Julia Zeitlinger, Justin Crocker, Juan Ignacio Fuxman Bass

引用次数: 0