Cell Systems最新文献_第5页

PocketAnchor: Learning structure-based pocket representations for protein-ligand interaction prediction. PocketAnchor:学习基于结构的口袋表示，用于蛋白质-配体相互作用预测。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-07-01 DOI: 10.2139/ssrn.4161090

Shuya Li, Tingzhong Tian, Ziting Zhang, Ziheng Zou, Dan Zhao, Jianyang Zeng

{"title":"PocketAnchor: Learning structure-based pocket representations for protein-ligand interaction prediction.","authors":"Shuya Li, Tingzhong Tian, Ziting Zhang, Ziheng Zou, Dan Zhao, Jianyang Zeng","doi":"10.2139/ssrn.4161090","DOIUrl":"https://doi.org/10.2139/ssrn.4161090","url":null,"abstract":"Protein-ligand interactions are essential for cellular activities and drug discovery processes. Appropriately and effectively representing protein features is of vital importance for developing computational approaches, especially data-driven methods, for predicting protein-ligand interactions. However, existing approaches may not fully investigate the features of the ligand-occupying regions in the protein pockets. Here, we design a structure-based protein representation method, named PocketAnchor, for capturing the local environmental and spatial features of protein pockets to facilitate protein-ligand interaction-related learning tasks. We define \"anchors\" as probe points reaching into the cavities and those located near the surface of proteins, and we design a specific message passing strategy for gathering local information from the atoms and surface neighboring these anchors. Comprehensive evaluation of our method demonstrated its successful applications in pocket detection and binding affinity prediction, which indicated that our anchor-based approach can provide effective protein feature representations for improving the prediction of protein-ligand interactions.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"1 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47292394","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: 0

The time-resolved genomic impact of Wnt/β-catenin signaling. Wnt/β-catenin信号传导的时间分辨基因组影响。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-07-01 DOI: 10.2139/ssrn.4208342

P. Pagella, Simon Söderholm, A. Nordin, Gianluca Zambanini, Valeria Ghezzi, Amaia Jauregi-Miguel, C. Cantú

{"title":"The time-resolved genomic impact of Wnt/β-catenin signaling.","authors":"P. Pagella, Simon Söderholm, A. Nordin, Gianluca Zambanini, Valeria Ghezzi, Amaia Jauregi-Miguel, C. Cantú","doi":"10.2139/ssrn.4208342","DOIUrl":"https://doi.org/10.2139/ssrn.4208342","url":null,"abstract":"Wnt signaling orchestrates gene expression via its effector, β-catenin. However, it is unknown whether β-catenin binds its target genomic regions simultaneously and how this impacts chromatin dynamics to modulate cell behavior. Using a combination of time-resolved CUT&RUN against β-catenin, ATAC-seq, and perturbation assays in different cell types, we show that Wnt/β-catenin physical targets are tissue-specific, β-catenin \"moves\" on different loci over time, and its association to DNA accompanies changing chromatin accessibility landscapes that determine cell behavior. In particular, Wnt/β-catenin progressively shapes the chromatin of human embryonic stem cells (hESCs) as they undergo mesodermal differentiation, a behavior that we define as \"plastic.\" In HEK293T cells, on the other hand, Wnt/β-catenin drives a transient chromatin opening, followed by re-establishment of the pre-stimulation state, a response that we define as \"elastic.\" Future experiments shall assess whether other cell communication mechanisms, in addition to Wnt signaling, are ruled by time, cellular idiosyncrasies, and chromatin constraints. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 7 1","pages":"563-581.e7"},"PeriodicalIF":9.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48221178","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: 4

A multi-scale map of protein assemblies in the DNA damage response. DNA 损伤反应中蛋白质组装的多尺度图谱。

IF 9 1区生物学

Cell Systems Pub Date : 2023-06-21 Epub Date: 2023-05-22 DOI: 10.1016/j.cels.2023.04.007

Anton Kratz, Minkyu Kim, Marcus R Kelly, Fan Zheng, Christopher A Koczor, Jianfeng Li, Keiichiro Ono, Yue Qin, Christopher Churas, Jing Chen, Rudolf T Pillich, Jisoo Park, Maya Modak, Rachel Collier, Kate Licon, Dexter Pratt, Robert W Sobol, Nevan J Krogan, Trey Ideker

{"title":"A multi-scale map of protein assemblies in the DNA damage response.","authors":"Anton Kratz, Minkyu Kim, Marcus R Kelly, Fan Zheng, Christopher A Koczor, Jianfeng Li, Keiichiro Ono, Yue Qin, Christopher Churas, Jing Chen, Rudolf T Pillich, Jisoo Park, Maya Modak, Rachel Collier, Kate Licon, Dexter Pratt, Robert W Sobol, Nevan J Krogan, Trey Ideker","doi":"10.1016/j.cels.2023.04.007","DOIUrl":"10.1016/j.cels.2023.04.007","url":null,"abstract":"The DNA damage response (DDR) ensures error-free DNA replication and transcription and is disrupted in numerous diseases. An ongoing challenge is to determine the proteins orchestrating DDR and their organization into complexes, including constitutive interactions and those responding to genomic insult. Here, we use multi-conditional network analysis to systematically map DDR assemblies at multiple scales. Affinity purifications of 21 DDR proteins, with/without genotoxin exposure, are combined with multi-omics data to reveal a hierarchical organization of 605 proteins into 109 assemblies. The map captures canonical repair mechanisms and proposes new DDR-associated proteins extending to stress, transport, and chromatin functions. We find that protein assemblies closely align with genetic dependencies in processing specific genotoxins and that proteins in multiple assemblies typically act in multiple genotoxin responses. Follow-up by DDR functional readouts newly implicates 12 assembly members in double-strand-break repair. The DNA damage response assemblies map is available for interactive visualization and query (ccmi.org/ddram/).","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 6","pages":"447-463.e8"},"PeriodicalIF":9.0,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9822780","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

Positional influence on cellular transcriptional identity revealed through spatially segmented single-cell transcriptomics. 通过空间分割的单细胞转录组学揭示了位置对细胞转录特性的影响。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-06-21 DOI: 10.1016/j.cels.2023.05.003

David B Morse, Aleksandra M Michalowski, Michele Ceribelli, Joachim De Jonghe, Maria Vias, Deanna Riley, Theresa Davies-Hill, Ty Voss, Stefania Pittaluga, Christoph Muus, Jiamin Liu, Samantha Boyle, David A Weitz, James D Brenton, Jason D Buenrostro, Tuomas P J Knowles, Craig J Thomas

{"title":"Positional influence on cellular transcriptional identity revealed through spatially segmented single-cell transcriptomics.","authors":"David B Morse, Aleksandra M Michalowski, Michele Ceribelli, Joachim De Jonghe, Maria Vias, Deanna Riley, Theresa Davies-Hill, Ty Voss, Stefania Pittaluga, Christoph Muus, Jiamin Liu, Samantha Boyle, David A Weitz, James D Brenton, Jason D Buenrostro, Tuomas P J Knowles, Craig J Thomas","doi":"10.1016/j.cels.2023.05.003","DOIUrl":"10.1016/j.cels.2023.05.003","url":null,"abstract":"Single-cell RNA sequencing (scRNA-seq) is a powerful technique for describing cell states. Identifying the spatial arrangement of these states in tissues remains challenging, with the existing methods requiring niche methodologies and expertise. Here, we describe segmentation by exogenous perfusion (SEEP), a rapid and integrated method to link surface proximity and environment accessibility to transcriptional identity within three-dimensional (3D) disease models. The method utilizes the steady-state diffusion kinetics of a fluorescent dye to establish a gradient along the radial axis of disease models. Classification of sample layers based on dye accessibility enables dissociated and sorted cells to be characterized by transcriptomic and regional identities. Using SEEP, we analyze spheroid, organoid, and in vivo tumor models of high-grade serous ovarian cancer (HGSOC). The results validate long-standing beliefs about the relationship between cell state and position while revealing new concepts regarding how spatially unique microenvironments influence the identity of individual cells within tumors.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 6","pages":"464-481.e7"},"PeriodicalIF":9.3,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10424188/pdf/nihms-1904912.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10006710","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

Single-cell A/B testing for cell-cell communication. 用于蜂窝通信的单蜂窝 A/B 测试。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-06-21 DOI: 10.1016/j.cels.2023.05.006

Caitlin M Aamodt, Nathan E Lewis

引用次数: 0

BioAutoMATED: An end-to-end automated machine learning tool for explanation and design of biological sequences. BioAutoMATED:一个端到端的自动化机器学习工具，用于解释和设计生物序列。

IF 9 1区生物学

Cell Systems Pub Date : 2023-06-21 DOI: 10.1016/j.cels.2023.05.007

Jacqueline A Valeri, Luis R Soenksen, Katherine M Collins, Pradeep Ramesh, George Cai, Rani Powers, Nicolaas M Angenent-Mari, Diogo M Camacho, Felix Wong, Timothy K Lu, James J Collins

{"title":"BioAutoMATED: An end-to-end automated machine learning tool for explanation and design of biological sequences.","authors":"Jacqueline A Valeri, Luis R Soenksen, Katherine M Collins, Pradeep Ramesh, George Cai, Rani Powers, Nicolaas M Angenent-Mari, Diogo M Camacho, Felix Wong, Timothy K Lu, James J Collins","doi":"10.1016/j.cels.2023.05.007","DOIUrl":"10.1016/j.cels.2023.05.007","url":null,"abstract":"The design choices underlying machine-learning (ML) models present important barriers to entry for many biologists who aim to incorporate ML in their research. Automated machine-learning (AutoML) algorithms can address many challenges that come with applying ML to the life sciences. However, these algorithms are rarely used in systems and synthetic biology studies because they typically do not explicitly handle biological sequences (e.g., nucleotide, amino acid, or glycan sequences) and cannot be easily compared with other AutoML algorithms. Here, we present BioAutoMATED, an AutoML platform for biological sequence analysis that integrates multiple AutoML methods into a unified framework. Users are automatically provided with relevant techniques for analyzing, interpreting, and designing biological sequences. BioAutoMATED predicts gene regulation, peptide-drug interactions, and glycan annotation, and designs optimized synthetic biology components, revealing salient sequence characteristics. By automating sequence modeling, BioAutoMATED allows life scientists to incorporate ML more readily into their work.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 6","pages":"525-542.e9"},"PeriodicalIF":9.0,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10700034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9682865","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

Redesign of an Escherichia coli Nissle treatment for phenylketonuria using insulated genomic landing pads and genetic circuits to reduce burden. 利用绝缘基因组着陆垫和基因电路重新设计治疗苯丙酮尿症的大肠杆菌尼氏疗法，以减轻负担。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-06-21 DOI: 10.1016/j.cels.2023.05.004

Alexander J Triassi, Brandon D Fields, Catherine E Monahan, Jillian M Means, Yongjin Park, Hamid Doosthosseini, Jai P Padmakumar, Vincent M Isabella, Christopher A Voigt

{"title":"Redesign of an Escherichia coli Nissle treatment for phenylketonuria using insulated genomic landing pads and genetic circuits to reduce burden.","authors":"Alexander J Triassi, Brandon D Fields, Catherine E Monahan, Jillian M Means, Yongjin Park, Hamid Doosthosseini, Jai P Padmakumar, Vincent M Isabella, Christopher A Voigt","doi":"10.1016/j.cels.2023.05.004","DOIUrl":"10.1016/j.cels.2023.05.004","url":null,"abstract":"To build therapeutic strains, Escherichia coli Nissle (EcN) have been engineered to express antibiotics, toxin-degrading enzymes, immunoregulators, and anti-cancer chemotherapies. For efficacy, the recombinant genes need to be highly expressed, but this imposes a burden on the cell, and plasmids are difficult to maintain in the body. To address these problems, we have developed landing pads in the EcN genome and genetic circuits to control therapeutic gene expression. These tools were applied to EcN SYNB1618, undergoing clinical trials as a phenylketonuria treatment. The pathway for converting phenylalanine to trans-cinnamic acid was moved to a landing pad under the control of a circuit that keeps the pathway off during storage. The resulting strain (EcN SYN8784) achieved higher activity than EcN SYNB1618, reaching levels near when the pathway is carried on a plasmid. This work demonstrates a simple system for engineering EcN that aids quantitative strain design for therapeutics.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 6","pages":"512-524.e12"},"PeriodicalIF":9.3,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9688760","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: 0

The trans-regulatory landscape of gene networks in plants. 植物基因网络的跨调控格局。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-06-21 DOI: 10.1016/j.cels.2023.05.002

Niklas F C Hummel, Andy Zhou, Baohua Li, Kasey Markel, Izaiah J Ornelas, Patrick M Shih

引用次数: 0

The computational capabilities of many-to-many protein interaction networks. 多对多蛋白质相互作用网络的计算能力。

IF 9 1区生物学

Cell Systems Pub Date : 2023-06-21 DOI: 10.1016/j.cels.2023.05.001

Heidi E Klumpe, Jordi Garcia-Ojalvo, Michael B Elowitz, Yaron E Antebi

引用次数: 0

High-throughput discovery and characterization of viral transcriptional effectors in human cells. 人类细胞中病毒转录效应物的高通量发现和表征。

IF 9 1区生物学

Cell Systems Pub Date : 2023-06-21 DOI: 10.1016/j.cels.2023.05.008

Connor H Ludwig, Abby R Thurm, David W Morgens, Kevin J Yang, Josh Tycko, Michael C Bassik, Britt A Glaunsinger, Lacramioara Bintu

{"title":"High-throughput discovery and characterization of viral transcriptional effectors in human cells.","authors":"Connor H Ludwig, Abby R Thurm, David W Morgens, Kevin J Yang, Josh Tycko, Michael C Bassik, Britt A Glaunsinger, Lacramioara Bintu","doi":"10.1016/j.cels.2023.05.008","DOIUrl":"10.1016/j.cels.2023.05.008","url":null,"abstract":"Viruses encode transcriptional regulatory proteins critical for controlling viral and host gene expression. Given their multifunctional nature and high sequence divergence, it is unclear which viral proteins can affect transcription and which specific sequences contribute to this function. Using a high-throughput assay, we measured the transcriptional regulatory potential of over 60,000 protein tiles across ∼1,500 proteins from 11 coronaviruses and all nine human herpesviruses. We discovered hundreds of transcriptional effector domains, including a conserved repression domain in all coronavirus Spike homologs, dual activation-repression domains in viral interferon regulatory factors (VIRFs), and an activation domain in six herpesvirus homologs of the single-stranded DNA-binding protein that we show is important for viral replication and late gene expression in Kaposi's sarcoma-associated herpesvirus (KSHV). For the effector domains we identified, we investigated their mechanisms via high-throughput sequence and chemical perturbations, pinpointing sequence motifs essential for function. This work massively expands viral protein annotations, serving as a springboard for studying their biological and health implications and providing new candidates for compact gene regulation tools.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 6","pages":"482-500.e8"},"PeriodicalIF":9.0,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10157442","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