Cell systems最新文献_第8页

Reconstructing developmental trajectories using latent dynamical systems and time-resolved transcriptomics. 利用潜在动力系统和时间分辨转录组学重建发育轨迹

Cell systems Pub Date : 2024-05-15 DOI: 10.1016/j.cels.2024.04.004

Rory J Maizels, Daniel M Snell, James Briscoe

{"title":"Reconstructing developmental trajectories using latent dynamical systems and time-resolved transcriptomics.","authors":"Rory J Maizels, Daniel M Snell, James Briscoe","doi":"10.1016/j.cels.2024.04.004","DOIUrl":"https://doi.org/10.1016/j.cels.2024.04.004","url":null,"abstract":"The snapshot nature of single-cell transcriptomics presents a challenge for studying the dynamics of cell fate decisions. Metabolic labeling and splicing can provide temporal information at single-cell level, but current methods have limitations. Here, we present a framework that overcomes these limitations: experimentally, we developed sci-FATE2, an optimized method for metabolic labeling with increased data quality, which we used to profile 45,000 embryonic stem (ES) cells differentiating into neural tube identities. Computationally, we developed a two-stage framework for dynamical modeling: VelvetVAE, a variational autoencoder (VAE) for velocity inference that outperforms all other tools tested, and VelvetSDE, a neural stochastic differential equation (nSDE) framework for simulating trajectory distributions. These recapitulate underlying dataset distributions and capture features such as decision boundaries between alternative fates and fate-specific gene expression. These methods recast single-cell analyses from descriptions of observed data to models of the dynamics that generated them, providing a framework for investigating developmental fate decisions.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 5","pages":"411-424.e9"},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961144","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

Causal gene regulatory analysis with RNA velocity reveals an interplay between slow and fast transcription factors. 利用 RNA 速度进行的因果基因调控分析揭示了慢速和快速转录因子之间的相互作用。

Cell systems Pub Date : 2024-05-15 DOI: 10.1016/j.cels.2024.04.005

Rohit Singh, Alexander P Wu, Anish Mudide, Bonnie Berger

{"title":"Causal gene regulatory analysis with RNA velocity reveals an interplay between slow and fast transcription factors.","authors":"Rohit Singh, Alexander P Wu, Anish Mudide, Bonnie Berger","doi":"10.1016/j.cels.2024.04.005","DOIUrl":"https://doi.org/10.1016/j.cels.2024.04.005","url":null,"abstract":"Single-cell expression dynamics, from differentiation trajectories or RNA velocity, have the potential to reveal causal links between transcription factors (TFs) and their target genes in gene regulatory networks (GRNs). However, existing methods either overlook these expression dynamics or necessitate that cells be ordered along a linear pseudotemporal axis, which is incompatible with branching trajectories. We introduce Velorama, an approach to causal GRN inference that represents single-cell differentiation dynamics as a directed acyclic graph of cells, constructed from pseudotime or RNA velocity measurements. Additionally, Velorama enables the estimation of the speed at which TFs influence target genes. Applying Velorama, we uncover evidence that the speed of a TF's interactions is tied to its regulatory function. For human corticogenesis, we find that slow TFs are linked to gliomas, while fast TFs are associated with neuropsychiatric diseases. We expect Velorama to become a critical part of the RNA velocity toolkit for investigating the causal drivers of differentiation and disease.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 5","pages":"462-474.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961140","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

Reconstructing developmental trajectories using latent dynamical systems and time-resolved transcriptomics. 利用潜在动力系统和时间分辨转录组学重建发育轨迹

Cell systems Pub Date : 2024-05-01 DOI: 10.1016/j.cels.2024.04.004

R. Maizels, Daniel M Snell, James Briscoe

引用次数: 0

Accurate single-molecule spot detection for image-based spatial transcriptomics with weakly supervised deep learning. 利用弱监督深度学习为基于图像的空间转录组学提供精确的单分子点检测。

Cell systems Pub Date : 2024-05-01 DOI: 10.1016/j.cels.2024.04.006

Emily Laubscher, X. Wang, Nitzan Razin, Tom Dougherty, Rosalind J. Xu, Lincoln Ombelets, Edward Pao, William Graf, Jeffrey R. Moffitt, Yisong Yue, David Van Valen

引用次数: 0

Multilevel relations among plankton stitched together with an eco-evolutionary needle. 用生态进化针缝合浮游生物之间的多层次关系。

Cell systems Pub Date : 2024-05-01 DOI: 10.1016/j.cels.2024.04.007

Van M. Savage

引用次数: 0

Rugged fitness landscapes minimize promiscuity in the evolution of transcriptional repressors. 在转录抑制因子的进化过程中，崎岖的适应性景观将杂交性降到最低。

Cell systems Pub Date : 2024-04-17 Epub Date: 2024-03-26 DOI: 10.1016/j.cels.2024.03.002

Anthony T Meger, Matthew A Spence, Mahakaran Sandhu, Dana Matthews, Jackie Chen, Colin J Jackson, Srivatsan Raman

{"title":"Rugged fitness landscapes minimize promiscuity in the evolution of transcriptional repressors.","authors":"Anthony T Meger, Matthew A Spence, Mahakaran Sandhu, Dana Matthews, Jackie Chen, Colin J Jackson, Srivatsan Raman","doi":"10.1016/j.cels.2024.03.002","DOIUrl":"10.1016/j.cels.2024.03.002","url":null,"abstract":"How a protein's function influences the shape of its fitness landscape, smooth or rugged, is a fundamental question in evolutionary biochemistry. Smooth landscapes arise when incremental mutational steps lead to a progressive change in function, as commonly seen in enzymes and binding proteins. On the other hand, rugged landscapes are poorly understood because of the inherent unpredictability of how sequence changes affect function. Here, we experimentally characterize the entire sequence phylogeny, comprising 1,158 extant and ancestral sequences, of the DNA-binding domain (DBD) of the LacI/GalR transcriptional repressor family. Our analysis revealed an extremely rugged landscape with rapid switching of specificity, even between adjacent nodes. Further, the ruggedness arises due to the necessity of the repressor to simultaneously evolve specificity for asymmetric operators and disfavors potentially adverse regulatory crosstalk. Our study provides fundamental insight into evolutionary, molecular, and biophysical rules of genetic regulation through the lens of fitness landscapes.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"374-387.e6"},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308242","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

A map of signaling responses in the human airway epithelium. 人类气道上皮细胞信号反应图。

Cell systems Pub Date : 2024-04-17 Epub Date: 2024-03-19 DOI: 10.1016/j.cels.2024.02.005

Katherine B McCauley, Kalki Kukreja, Alfredo E Tovar Walker, Aron B Jaffe, Allon M Klein

{"title":"A map of signaling responses in the human airway epithelium.","authors":"Katherine B McCauley, Kalki Kukreja, Alfredo E Tovar Walker, Aron B Jaffe, Allon M Klein","doi":"10.1016/j.cels.2024.02.005","DOIUrl":"10.1016/j.cels.2024.02.005","url":null,"abstract":"Receptor-mediated signaling plays a central role in tissue regeneration, and it is dysregulated in disease. Here, we build a signaling-response map for a model regenerative human tissue: the airway epithelium. We analyzed the effect of 17 receptor-mediated signaling pathways on organotypic cultures to determine changes in abundance and phenotype of epithelial cell types. This map recapitulates the gamut of known airway epithelial signaling responses to these pathways. It defines convergent states induced by multiple ligands and diverse, ligand-specific responses in basal cell and secretory cell metaplasia. We show that loss of canonical differentiation induced by multiple pathways is associated with cell-cycle arrest, but that arrest is not sufficient to block differentiation. Using the signaling-response map, we show that a TGFB1-mediated response underlies specific aberrant cells found in multiple lung diseases and identify interferon responses in COVID-19 patient samples. Thus, we offer a framework enabling systematic evaluation of tissue signaling responses. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"307-321.e10"},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11031335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178236","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

The electrostatic landscape of MHC-peptide binding revealed using inception networks. 利用起始网络揭示 MHC 肽结合的静电景观。

Cell systems Pub Date : 2024-04-17 Epub Date: 2024-03-29 DOI: 10.1016/j.cels.2024.03.001

Eric Wilson, John Kevin Cava, Diego Chowell, Remya Raja, Kiran K Mangalaparthi, Akhilesh Pandey, Marion Curtis, Karen S Anderson, Abhishek Singharoy

{"title":"The electrostatic landscape of MHC-peptide binding revealed using inception networks.","authors":"Eric Wilson, John Kevin Cava, Diego Chowell, Remya Raja, Kiran K Mangalaparthi, Akhilesh Pandey, Marion Curtis, Karen S Anderson, Abhishek Singharoy","doi":"10.1016/j.cels.2024.03.001","DOIUrl":"10.1016/j.cels.2024.03.001","url":null,"abstract":"Predictive modeling of macromolecular recognition and protein-protein complementarity represents one of the cornerstones of biophysical sciences. However, such models are often hindered by the combinatorial complexity of interactions at the molecular interfaces. Exemplary of this problem is peptide presentation by the highly polymorphic major histocompatibility complex class I (MHC-I) molecule, a principal component of immune recognition. We developed human leukocyte antigen (HLA)-Inception, a deep biophysical convolutional neural network, which integrates molecular electrostatics to capture non-bonded interactions for predicting peptide binding motifs across 5,821 MHC-I alleles. These predictions of generated motifs correlate strongly with experimental peptide binding and presentation data. Beyond molecular interactions, the study demonstrates the application of predicted motifs in analyzing MHC-I allele associations with HIV disease progression and patient response to immune checkpoint inhibitors. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"362-373.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330355","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

Cross-evaluation of E. coli's operon structures via a whole-cell model suggests alternative cellular benefits for low- versus high-expressing operons. 通过全细胞模型对大肠杆菌操作子结构的交叉评估表明，低表达操作子和高表达操作子在细胞中具有不同的益处。

Cell systems Pub Date : 2024-03-20 Epub Date: 2024-02-27 DOI: 10.1016/j.cels.2024.02.002

Gwanggyu Sun, Mialy M DeFelice, Taryn E Gillies, Travis A Ahn-Horst, Cecelia J Andrews, Markus Krummenacker, Peter D Karp, Jerry H Morrison, Markus W Covert

{"title":"Cross-evaluation of E. coli's operon structures via a whole-cell model suggests alternative cellular benefits for low- versus high-expressing operons.","authors":"Gwanggyu Sun, Mialy M DeFelice, Taryn E Gillies, Travis A Ahn-Horst, Cecelia J Andrews, Markus Krummenacker, Peter D Karp, Jerry H Morrison, Markus W Covert","doi":"10.1016/j.cels.2024.02.002","DOIUrl":"10.1016/j.cels.2024.02.002","url":null,"abstract":"Many bacteria use operons to coregulate genes, but it remains unclear how operons benefit bacteria. We integrated E. coli's 788 polycistronic operons and 1,231 transcription units into an existing whole-cell model and found inconsistencies between the proposed operon structures and the RNA-seq read counts that the model was parameterized from. We resolved these inconsistencies through iterative, model-guided corrections to both datasets, including the correction of RNA-seq counts of short genes that were misreported as zero by existing alignment algorithms. The resulting model suggested two main modes by which operons benefit bacteria. For 86% of low-expression operons, adding operons increased the co-expression probabilities of their constituent proteins, whereas for 92% of high-expression operons, adding operons resulted in more stable expression ratios between the proteins. These simulations underscored the need for further experimental work on how operons reduce noise and synchronize both the expression timing and the quantity of constituent genes. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"227-245.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10957310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992088","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

High immigration rates critical for establishing emigration-driven diversity in microbial communities. 高移民率对于在微生物群落中建立移民驱动的多样性至关重要。

Cell systems Pub Date : 2024-03-20 Epub Date: 2024-02-23 DOI: 10.1016/j.cels.2024.02.001

Xiaoli Chen, Miaoxiao Wang, Laipeng Luo, Liyun An, Xiaonan Liu, Yuan Fang, Ting Huang, Yong Nie, Xiao-Lei Wu

引用次数: 0