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Dynamic models for metabolomics data integration 代谢组学数据整合的动态模型
IF 3.7
Current Opinion in Systems Biology Pub Date : 2021-12-01 DOI: 10.1016/j.coisb.2021.100358
Polina Lakrisenko , Daniel Weindl
{"title":"Dynamic models for metabolomics data integration","authors":"Polina Lakrisenko ,&nbsp;Daniel Weindl","doi":"10.1016/j.coisb.2021.100358","DOIUrl":"10.1016/j.coisb.2021.100358","url":null,"abstract":"<div><p>As metabolomics datasets are becoming larger and more complex, there is an increasing need for model-based data integration and analysis to optimally leverage these data. Dynamic models of metabolism allow for the integration of heterogeneous data and the analysis of dynamic phenotypes. Here, we review recent efforts in using dynamic metabolic models for data integration, focusing on approaches based on ordinary differential equations that are applicable to both time-resolved and steady-state measurements and that do not require flux distributions as inputs. Furthermore, we discuss recent advances and current challenges. We conclude that much progress has been made in various areas, such as the development of scalable simulation tools, and although challenges remain, dynamic modeling is a powerful tool for metabolomics data analysis that is not yet living up to its full potential.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"28 ","pages":"Article 100358"},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.coisb.2021.100358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44755827","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: 2
Engineering programmable RNA synthetic circuits in mammalian cells 在哺乳动物细胞中设计可编程RNA合成电路
IF 3.7
Current Opinion in Systems Biology Pub Date : 2021-12-01 DOI: 10.1016/j.coisb.2021.100395
Federica Cella, Ilaria De Martino , Francesca Piro , Velia Siciliano
{"title":"Engineering programmable RNA synthetic circuits in mammalian cells","authors":"Federica Cella,&nbsp;Ilaria De Martino ,&nbsp;Francesca Piro ,&nbsp;Velia Siciliano","doi":"10.1016/j.coisb.2021.100395","DOIUrl":"10.1016/j.coisb.2021.100395","url":null,"abstract":"<div><p><span>The ability to reprogram mammalian cells with tight spatiotemporal control </span>over gene expression<span> and cell response has provided a powerful means to address biomedical challenges. To provide safer synthetic biology products, RNA<span> has recently emerged as an alternative to DNA to deliver transgenes into mammalian cells. In this review, we discuss recent tools implemented to engineer programmable RNA-based synthetic circuits in mammalian cells. We examine the limitations of RNA-encoded gene delivery, and we highlight significant studies that successfully improved payloads expression and persistence and maximized RNA delivery efficiency. Finally, we conclude by discussing examples of RNA-based therapeutics and future perspectives.</span></span></p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"28 ","pages":"Article 100395"},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49554071","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
Metabolism as a signal generator in bacteria 作为细菌信号发生器的新陈代谢
IF 3.7
Current Opinion in Systems Biology Pub Date : 2021-12-01 DOI: 10.1016/j.coisb.2021.100404
Daniela Ledezma-Tejeida , Evgeniya Schastnaya , Uwe Sauer
{"title":"Metabolism as a signal generator in bacteria","authors":"Daniela Ledezma-Tejeida ,&nbsp;Evgeniya Schastnaya ,&nbsp;Uwe Sauer","doi":"10.1016/j.coisb.2021.100404","DOIUrl":"10.1016/j.coisb.2021.100404","url":null,"abstract":"<div><p>Bacteria constantly monitor their environment to adapt their inner makeup. Beyond providing chemical sustenance, metabolism provides most of the feedback on the cellular environment via metabolite binding to regulatory proteins or mRNA. Although first metabolite-protein interactions were discovered more than 60 years ago, identification of new interactions is still technically challenging and time-consuming. Here, we compiled and quantified the current knowledge on metabolite-protein interactions and review recent advances in the identification of interactions and in understanding how metabolites act as signals to transcription factors, two-component systems, protein kinases, and riboswitches. New systematic methods of metabolite-protein identification and omics integration will accelerate the pace of discovery, a remaining challenge is understanding of functionality and the coordination of local and global metabolic signals across different regulatory layers.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"28 ","pages":"Article 100404"},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452310021000998/pdfft?md5=fbcde72423083c27973f1b0a79ce304b&pid=1-s2.0-S2452310021000998-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46324043","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: 4
Design of genetic circuits that are robust to resource competition 对资源竞争具有鲁棒性的遗传电路设计
IF 3.7
Current Opinion in Systems Biology Pub Date : 2021-12-01 DOI: 10.1016/j.coisb.2021.100357
Cameron D. McBride , Theodore W. Grunberg , Domitilla Del Vecchio
{"title":"Design of genetic circuits that are robust to resource competition","authors":"Cameron D. McBride ,&nbsp;Theodore W. Grunberg ,&nbsp;Domitilla Del Vecchio","doi":"10.1016/j.coisb.2021.100357","DOIUrl":"10.1016/j.coisb.2021.100357","url":null,"abstract":"<div><p>The ability to engineer genetic circuits in living cells has tremendous potential in many applications, from health, to energy, to bio-manufacturing. Although substantial efforts have gone into design approaches that make circuits robust to variable cellular context, context dependence of genetic circuits remains a significant hurdle. We review intra-cellular resource competition, one culprit of context dependence, and summarize recent efforts toward design approaches to mitigate it. We classify these approaches into two main groups: global control and local control. In the former, the pool of resources is regulated to meet the demand, and in the latter, individual modules are regulated to be robust to variability in the pool of resources. Within each group, we highlight both feedback and feedforward implementations.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"28 ","pages":"Article 100357"},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.coisb.2021.100357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47057967","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: 14
Multi-input biocomputer gene circuits for therapeutic application 用于治疗的多输入生物计算机基因电路
IF 3.7
Current Opinion in Systems Biology Pub Date : 2021-12-01 DOI: 10.1016/j.coisb.2021.100371
Judith Johanna Jaekel, David Schweingruber, Vasileios Cheras, Jiten Doshi, Yaakov Benenson
{"title":"Multi-input biocomputer gene circuits for therapeutic application","authors":"Judith Johanna Jaekel,&nbsp;David Schweingruber,&nbsp;Vasileios Cheras,&nbsp;Jiten Doshi,&nbsp;Yaakov Benenson","doi":"10.1016/j.coisb.2021.100371","DOIUrl":"10.1016/j.coisb.2021.100371","url":null,"abstract":"<div><p>Clinical approvals of gene and cell therapies in recent years, and advances in our ability to engineer complex cellular functions using synthetic biology have fueled interest in merging these two approaches to develop and deploy ever more sophisticated treatments. One area of interface between synthetic biology tools and therapeutics comprises synthetic gene circuits that ‘compute’ a response in a programmable fashion using multiple biomolecular inputs. The potential therapeutic utility of such circuits hinges on their ability to perform logical integration of inputs linked to the human cell phenotype. AND logic increases response specificity, OR logic enables targeting heterogeneous cell populations, and NOT logic provides additional safety. We review recent efforts to implement input sensing and logical integration capabilities in cell, gene, RNA, and microbiome-based therapies. With therapeutic candidates using biomolecular computation already in clinical trials, the approach is poised to revolutionize the field of advanced therapies in the years to come.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"28 ","pages":"Article 100371"},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.coisb.2021.100371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43649718","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: 1
Click it or stick it: Covalent and non-covalent methods for protein-self assembly 点击或粘贴:蛋白质自组装的共价和非共价方法
IF 3.7
Current Opinion in Systems Biology Pub Date : 2021-12-01 DOI: 10.1016/j.coisb.2021.100374
Oskar J. Lange, Karen M. Polizzi
{"title":"Click it or stick it: Covalent and non-covalent methods for protein-self assembly","authors":"Oskar J. Lange,&nbsp;Karen M. Polizzi","doi":"10.1016/j.coisb.2021.100374","DOIUrl":"10.1016/j.coisb.2021.100374","url":null,"abstract":"<div><p>Protein complexes<span> are ubiquitous in living systems and have a range of biotechnological applications. However, building protein structures from scratch can be a difficult and laborious process. Here, we review recent developments in protein self-assembly, including a range of tools for covalent and non-covalent assembly of protein structures with user-defined architectures. Key achievements in covalent protein assembly include the development of systems with fast reaction rates and nM affinities. Non-covalent assembly methods have lagged because of the complexity of natural interactions governing protein assembly; but recent developments have created modular methods that are more broadly applicable. On the horizon, we foresee an increasing role for computational protein design tools as key in cementing the role of applications, as opposed to methodology, as the main driving force of research in this field.</span></p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"28 ","pages":"Article 100374"},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.coisb.2021.100374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48136963","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: 3
Control of mammalian cell-based devices with genetic programming 用遗传程序控制哺乳动物细胞为基础的装置
IF 3.7
Current Opinion in Systems Biology Pub Date : 2021-12-01 DOI: 10.1016/j.coisb.2021.100372
Kate E. Dray , Hailey I. Edelstein , Kathleen S. Dreyer , Joshua N. Leonard
{"title":"Control of mammalian cell-based devices with genetic programming","authors":"Kate E. Dray ,&nbsp;Hailey I. Edelstein ,&nbsp;Kathleen S. Dreyer ,&nbsp;Joshua N. Leonard","doi":"10.1016/j.coisb.2021.100372","DOIUrl":"10.1016/j.coisb.2021.100372","url":null,"abstract":"<div><p><span>Synthetic biology increasingly enables the construction of sophisticated functions in mammalian cells. A particularly promising frontier combines concepts drawn from industrial process control engineering — which is used to confer and balance properties such as stability and efficiency — with understanding as to how living systems have evolved to perform similar tasks with biological components. In this review, we first survey the state-of-the-art for both technologies and strategies available for </span>genetic programming in mammalian cells. We then discuss recent progress in implementing programming objectives inspired by engineered and natural control mechanisms. Finally, we consider the transformative role of model-guided design in the present and future construction of customized mammalian cell functions for applications in biotechnology, medicine, and fundamental research.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"28 ","pages":"Article 100372"},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.coisb.2021.100372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39420648","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: 1
Systems biology at the giga-scale: Large multiscale models of complex, heterogeneous multicellular systems 千兆级的系统生物学:复杂、异质多细胞系统的大型多尺度模型
IF 3.7
Current Opinion in Systems Biology Pub Date : 2021-12-01 DOI: 10.1016/j.coisb.2021.100385
Arnau Montagud , Miguel Ponce-de-Leon , Alfonso Valencia
{"title":"Systems biology at the giga-scale: Large multiscale models of complex, heterogeneous multicellular systems","authors":"Arnau Montagud ,&nbsp;Miguel Ponce-de-Leon ,&nbsp;Alfonso Valencia","doi":"10.1016/j.coisb.2021.100385","DOIUrl":"10.1016/j.coisb.2021.100385","url":null,"abstract":"<div><p>Agent-based modelling has proven its usefulness in several biomedical projects by explaining and uncovering mechanisms in diseases. Nevertheless, the scenarios addressed in these models usually consider a small number of cells, lack cell-specific characterisation and dynamic interactions and have a simplistic environment description. Tools that enable scalable, real-sized simulations of biological systems that require complex setups are needed to have simulations closer to biomedical scenarios that can capture cell-to-cell heterogeneity and system-wide emerging properties. To deliver simulations at the giga-scale (10<sup>9</sup> cells), different tools have implemented technologies to run in high-performance computing clusters. We hereby review these efforts and detail the main areas of improvement the field needs to focus on to have simulations that are a step closer to having digital twins.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"28 ","pages":"Article 100385"},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452310021000792/pdfft?md5=7797269073a56e3d5733626dc36a5f79&pid=1-s2.0-S2452310021000792-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42512765","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: 18
Mechanistic models of blood cell fate decisions in the era of single-cell data 单细胞数据时代血细胞命运决定的机制模型
IF 3.7
Current Opinion in Systems Biology Pub Date : 2021-12-01 DOI: 10.1016/j.coisb.2021.100355
Ingmar Glauche , Carsten Marr
{"title":"Mechanistic models of blood cell fate decisions in the era of single-cell data","authors":"Ingmar Glauche ,&nbsp;Carsten Marr","doi":"10.1016/j.coisb.2021.100355","DOIUrl":"10.1016/j.coisb.2021.100355","url":null,"abstract":"<div><p>Billions of functionally distinct blood cells emerge from a pool of hematopoietic stem cells in our bodies every day. This progressive differentiation process is hierarchically structured and remarkably robust. We provide an introductory review to mathematical approaches addressing the functional aspects of how lineage choice is potentially implemented on a molecular level. Emerging from studies on the mutual repression of key transcription factors, we illustrate how those simple concepts have been challenged in recent years and subsequently extended. Especially, the analysis of omics data on the single-cell level with computational tools provides descriptive insights on a yet unknown level, while their embedding into a consistent mechanistic and mathematical framework is still incomplete.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"28 ","pages":"Article 100355"},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.coisb.2021.100355","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39761096","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: 2
External control of microbial populations for bioproduction: A modeling and optimization viewpoint 生物生产中微生物种群的外部控制:建模和优化观点
IF 3.7
Current Opinion in Systems Biology Pub Date : 2021-12-01 DOI: 10.1016/j.coisb.2021.100394
François Bertaux , Jakob Ruess , Grégory Batt
{"title":"External control of microbial populations for bioproduction: A modeling and optimization viewpoint","authors":"François Bertaux ,&nbsp;Jakob Ruess ,&nbsp;Grégory Batt","doi":"10.1016/j.coisb.2021.100394","DOIUrl":"10.1016/j.coisb.2021.100394","url":null,"abstract":"<div><p>When engineering microbes for bioproduction, one is necessarily confronted with the existing tradeoff between efficient bioproduction and maintenance of the cell physiology and growth. Moreover, because cellular processes at the single-cell level are coupled with population dynamics via selection mechanisms, this question should be investigated at the population level. Identifying the temporal induction profile that maximizes production in the long term is highly challenging. External control allows to dynamically adapt the strength of the induction from the outside based on intracellular readouts. It allows benchmarking various regulation functions and, coupled with modeling approaches, identifying and applying optimal strategies. In this review, we describe recent advances using quantitative approaches, modeling, and control theory that pave the way to compute external stimulations maximizing long-term production.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":"28 ","pages":"Article 100394"},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45785173","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: 3
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