Cell systems最新文献_第10页

A continuous epistasis model for predicting growth rate given combinatorial variation in gene expression and environment. 在基因表达和环境组合变化的情况下，预测生长率的连续外显模型。

Cell systems Pub Date : 2024-02-21 Epub Date: 2024-02-09 DOI: 10.1016/j.cels.2024.01.003

Ryan M Otto, Agata Turska-Nowak, Philip M Brown, Kimberly A Reynolds

{"title":"A continuous epistasis model for predicting growth rate given combinatorial variation in gene expression and environment.","authors":"Ryan M Otto, Agata Turska-Nowak, Philip M Brown, Kimberly A Reynolds","doi":"10.1016/j.cels.2024.01.003","DOIUrl":"10.1016/j.cels.2024.01.003","url":null,"abstract":"Quantifying and predicting growth rate phenotype given variation in gene expression and environment is complicated by epistatic interactions and the vast combinatorial space of possible perturbations. We developed an approach for mapping expression-growth rate landscapes that integrates sparsely sampled experimental measurements with an interpretable machine learning model. We used mismatch CRISPRi across pairs and triples of genes to create over 8,000 titrated changes in E. coli gene expression under varied environmental contexts, exploring epistasis in up to 22 distinct environments. Our results show that a pairwise model previously used to describe drug interactions well-described these data. The model yielded interpretable parameters related to pathway architecture and generalized to predict the combined effect of up to four perturbations when trained solely on pairwise perturbation data. We anticipate this approach will be broadly applicable in optimizing bacterial growth conditions, generating pharmacogenomic models, and understanding the fundamental constraints on bacterial gene expression. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"134-148.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10885703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716697","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

Single-cell colocalization analysis using a deep generative model. 利用深度生成模型进行单细胞共定位分析

Cell systems Pub Date : 2024-02-21 DOI: 10.1016/j.cels.2024.01.007

Yasuhiro Kojima, Shinji Mii, Shuto Hayashi, Haruka Hirose, Masato Ishikawa, Masashi Akiyama, Atsushi Enomoto, Teppei Shimamura

{"title":"Single-cell colocalization analysis using a deep generative model.","authors":"Yasuhiro Kojima, Shinji Mii, Shuto Hayashi, Haruka Hirose, Masato Ishikawa, Masashi Akiyama, Atsushi Enomoto, Teppei Shimamura","doi":"10.1016/j.cels.2024.01.007","DOIUrl":"10.1016/j.cels.2024.01.007","url":null,"abstract":"Analyzing colocalization of single cells with heterogeneous molecular phenotypes is essential for understanding cell-cell interactions, and cellular responses to external stimuli and their biological functions in diseases and tissues. However, existing computational methodologies identified the colocalization patterns between predefined cell populations, which can obscure the molecular signatures arising from intercellular communication. Here, we introduce DeepCOLOR, a computational framework based on a deep generative model that recovers intercellular colocalization networks with single-cell resolution by the integration of single-cell and spatial transcriptomes. Along with colocalized population detection accuracy that is superior to existing methods in simulated dataset, DeepCOLOR identified plausible cell-cell interaction candidates between colocalized single cells and segregated cell populations defined by the colocalization relationships in mouse brain tissues, human squamous cell carcinoma samples, and human lung tissues infected with SARS-CoV-2. DeepCOLOR is applicable to studying cell-cell interactions behind various spatial niches. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 2","pages":"180-192.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934738","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

Accurate top protein variant discovery via low-N pick-and-validate machine learning. 通过低 N 挑选和验证机器学习准确发现顶级蛋白质变体。

Cell systems Pub Date : 2024-02-21 Epub Date: 2024-02-09 DOI: 10.1016/j.cels.2024.01.002

Hoi Yee Chu, John H C Fong, Dawn G L Thean, Peng Zhou, Frederic K C Fung, Yuanhua Huang, Alan S L Wong

{"title":"Accurate top protein variant discovery via low-N pick-and-validate machine learning.","authors":"Hoi Yee Chu, John H C Fong, Dawn G L Thean, Peng Zhou, Frederic K C Fung, Yuanhua Huang, Alan S L Wong","doi":"10.1016/j.cels.2024.01.002","DOIUrl":"10.1016/j.cels.2024.01.002","url":null,"abstract":"A strategy to obtain the greatest number of best-performing variants with least amount of experimental effort over the vast combinatorial mutational landscape would have enormous utility in boosting resource producibility for protein engineering. Toward this goal, we present a simple and effective machine learning-based strategy that outperforms other state-of-the-art methods. Our strategy integrates zero-shot prediction and multi-round sampling to direct active learning via experimenting with only a few predicted top variants. We find that four rounds of low-N pick-and-validate sampling of 12 variants for machine learning yielded the best accuracy of up to 92.6% in selecting the true top 1% variants in combinatorial mutant libraries, whereas two rounds of 24 variants can also be used. We demonstrate our strategy in successfully discovering high-performance protein variants from diverse families including the CRISPR-based genome editors, supporting its generalizable application for solving protein engineering tasks. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"193-203.e6"},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716744","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

Clonally heritable gene expression imparts a layer of diversity within cell types. 克隆遗传的基因表达为细胞类型提供了一层多样性。

Cell systems Pub Date : 2024-02-21 Epub Date: 2024-02-09 DOI: 10.1016/j.cels.2024.01.004

Jeff E Mold, Martin H Weissman, Michael Ratz, Michael Hagemann-Jensen, Joanna Hård, Carl-Johan Eriksson, Hosein Toosi, Joseph Berghenstråhle, Christoph Ziegenhain, Leonie von Berlin, Marcel Martin, Kim Blom, Jens Lagergren, Joakim Lundeberg, Rickard Sandberg, Jakob Michaëlsson, Jonas Frisén

{"title":"Clonally heritable gene expression imparts a layer of diversity within cell types.","authors":"Jeff E Mold, Martin H Weissman, Michael Ratz, Michael Hagemann-Jensen, Joanna Hård, Carl-Johan Eriksson, Hosein Toosi, Joseph Berghenstråhle, Christoph Ziegenhain, Leonie von Berlin, Marcel Martin, Kim Blom, Jens Lagergren, Joakim Lundeberg, Rickard Sandberg, Jakob Michaëlsson, Jonas Frisén","doi":"10.1016/j.cels.2024.01.004","DOIUrl":"10.1016/j.cels.2024.01.004","url":null,"abstract":"Cell types can be classified according to shared patterns of transcription. Non-genetic variability among individual cells of the same type has been ascribed to stochastic transcriptional bursting and transient cell states. Using high-coverage single-cell RNA profiling, we asked whether long-term, heritable differences in gene expression can impart diversity within cells of the same type. Studying clonal human lymphocytes and mouse brain cells, we uncovered a vast diversity of heritable gene expression patterns among different clones of cells of the same type in vivo. We combined chromatin accessibility and RNA profiling on different lymphocyte clones to reveal thousands of regulatory regions exhibiting interclonal variation, which could be directly linked to interclonal variation in gene expression. Our findings identify a source of cellular diversity, which may have important implications for how cellular populations are shaped by selective processes in development, aging, and disease. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"149-165.e10"},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716745","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

Controlled exchange of protein and nucleic acid signals from and between synthetic minimal cells. 合成最小细胞之间蛋白质和核酸信号的可控交换。

Cell systems Pub Date : 2024-01-17 DOI: 10.1016/j.cels.2023.12.008

Joseph M Heili, Kaitlin Stokes, Nathaniel J Gaut, Christopher Deich, Judee Sharon, Tanner Hoog, Jose Gomez-Garcia, Brock Cash, Matthew R Pawlak, Aaron E Engelhart, Katarzyna P Adamala

{"title":"Controlled exchange of protein and nucleic acid signals from and between synthetic minimal cells.","authors":"Joseph M Heili, Kaitlin Stokes, Nathaniel J Gaut, Christopher Deich, Judee Sharon, Tanner Hoog, Jose Gomez-Garcia, Brock Cash, Matthew R Pawlak, Aaron E Engelhart, Katarzyna P Adamala","doi":"10.1016/j.cels.2023.12.008","DOIUrl":"10.1016/j.cels.2023.12.008","url":null,"abstract":"Synthetic minimal cells are a class of bioreactors that have some, but not all, functions of live cells. Here, we report a critical step toward the development of a bottom-up minimal cell: cellular export of functional protein and RNA products. We used cell-penetrating peptide tags to translocate payloads across a synthetic cell vesicle membrane. We demonstrated efficient transport of active enzymes and transport of nucleic acid payloads by RNA-binding proteins. We investigated influence of a concentration gradient alongside other factors on the efficiency of the translocation, and we show a method to increase product accumulation in one location. We demonstrate the use of this technology to engineer molecular communication between different populations of synthetic cells, to exchange protein and nucleic acid signals. The synthetic minimal cell production and export of proteins or nucleic acids allows experimental designs that approach the complexity and relevancy of natural biological systems. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 1","pages":"49-62.e4"},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492937","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

Modes and motifs in multicellular communication. 多细胞通讯的模式和主题。

Cell systems Pub Date : 2024-01-17 DOI: 10.1016/j.cels.2023.12.007

Anna C Kögler, Patrick Müller

引用次数: 0

Inference of differentiation trajectories by transfer learning across biological processes. 通过跨生物过程的迁移学习推断分化轨迹。

Cell systems Pub Date : 2024-01-17 Epub Date: 2023-12-20 DOI: 10.1016/j.cels.2023.12.002

Gaurav Jumde, Bastiaan Spanjaard, Jan Philipp Junker

引用次数: 0

The trade-off between individual metabolic specialization and versatility determines the metabolic efficiency of microbial communities. 个体代谢专业化与多功能性之间的权衡决定了微生物群落的代谢效率。

Cell systems Pub Date : 2024-01-17 DOI: 10.1016/j.cels.2023.12.004

Miaoxiao Wang, Xiaoli Chen, Yuan Fang, Xin Zheng, Ting Huang, Yong Nie, Xiao-Lei Wu

{"title":"The trade-off between individual metabolic specialization and versatility determines the metabolic efficiency of microbial communities.","authors":"Miaoxiao Wang, Xiaoli Chen, Yuan Fang, Xin Zheng, Ting Huang, Yong Nie, Xiao-Lei Wu","doi":"10.1016/j.cels.2023.12.004","DOIUrl":"10.1016/j.cels.2023.12.004","url":null,"abstract":"In microbial systems, a metabolic pathway can be either completed by one autonomous population or distributed among a consortium performing metabolic division of labor (MDOL). MDOL facilitates the system's function by reducing the metabolic burden; however, it may hinder the function by reducing the exchange efficiency of metabolic intermediates among individuals. As a result, the function of a community is influenced by the trade-offs between the metabolic specialization and versatility of individuals. To experimentally test this hypothesis, we deconstructed the naphthalene degradation pathway into four steps and introduced them individually or combinatorically into different strains with varying levels of metabolic specialization. Using these strains, we engineered 1,456 synthetic consortia and found that 74 consortia exhibited higher degradation function than both the autonomous population and rigorous MDOL consortium. Quantitative modeling provides general strategies for identifying the most effective MDOL configuration. Our study provides critical insights into the engineering of high-performance microbial systems.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 1","pages":"63-74.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492944","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

Meta learning addresses noisy and under-labeled data in machine learning-guided antibody engineering. 元学习可解决机器学习引导的抗体工程中的噪声和标记不足数据问题。

Cell systems Pub Date : 2024-01-17 Epub Date: 2024-01-08 DOI: 10.1016/j.cels.2023.12.003

Mason Minot, Sai T Reddy

引用次数: 0

Modeling elucidates context dependence in adipose regulation. 建模阐明了脂肪调节的环境依赖性。

Cell systems Pub Date : 2023-12-20 DOI: 10.1016/j.cels.2023.11.002

Cameron D Vasquez, John G Albeck

引用次数: 0