Frontiers in systems biology最新文献_第2页

Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapy 因特蛋白介导的甲状腺激素生物传感器：实现激素治疗的可控给药

Frontiers in systems biology Pub Date : 2024-04-03 DOI: 10.3389/fsysb.2024.1270071

Quim Martí-Baena, Andreu Pascuet-Fontanet, Tomas Berjaga-Buisan, Miriam Caravaca-Rodríguez, Jaume Puig-Costa-Jussà, A. Sanchez-Mejias, Dimitrije Ivančić, Sira Mogas-Díez, Marc Güell, Javier Macia

{"title":"Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapy","authors":"Quim Martí-Baena, Andreu Pascuet-Fontanet, Tomas Berjaga-Buisan, Miriam Caravaca-Rodríguez, Jaume Puig-Costa-Jussà, A. Sanchez-Mejias, Dimitrije Ivančić, Sira Mogas-Díez, Marc Güell, Javier Macia","doi":"10.3389/fsysb.2024.1270071","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1270071","url":null,"abstract":"Although blood sampling and medical imaging are well-established techniques in clinical diagnostics, they often require long post-processing procedures. Fast and simple quantification of signaling molecules can enable efficient health monitoring and improve diagnoses. Thyroid hormones (THs) treatment relies on trial-and-error dose adjustments, and requires constant tracking via blood tests. Thus, a fast and reliable method that can constantly track THs levels could substantially improve patient quality of life by reducing their visits to doctors. Synthetic biosensors have shown to be inexpensive and easy tools for sensing molecules, with their use in healthcare increasing over time. This study describes the construction of an engineered THs bacterial biosensor, consisting of a split-intein-based TH receptor ligand binding domain (LBD) biosensor that reconstitutes green fluorescence protein (GFP) after binding to TH. This biosensor could quantitatively measure THs concentrations by evaluating fluorescence intensity. In vitro sensing using Escherichia coli produced GFP over a wide dynamic range. The biosensor was further optimized by adding a double LBD, which enhanced its dynamic range until it reached healthy physiological conditions. Moreover, a mathematical model was developed to assess the dynamic properties of the biosensor and to provide a basis for the characterization of other intein-mediated biosensors. This type of biosensor can be used as the basis for novel treatments of thyroid diseases and can be adapted to measure the concentrations of other hormones, giving rise to a series of mathematically characterized modular biosensors.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140747759","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

In silico biomarker analysis of the adverse effects of perfluorooctane sulfonate (PFOS) exposure on the metabolic physiology of embryo-larval zebrafish 全氟辛烷磺酸（PFOS）暴露对斑马鱼胚胎-幼鱼代谢生理不良影响的硅学生物标志物分析

Frontiers in systems biology Pub Date : 2024-03-27 DOI: 10.3389/fsysb.2024.1367562

Rayna M Nolen, Lene H. Petersen, Karl Kaiser, Antonietta Quigg, D. Hala

{"title":"In silico biomarker analysis of the adverse effects of perfluorooctane sulfonate (PFOS) exposure on the metabolic physiology of embryo-larval zebrafish","authors":"Rayna M Nolen, Lene H. Petersen, Karl Kaiser, Antonietta Quigg, D. Hala","doi":"10.3389/fsysb.2024.1367562","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1367562","url":null,"abstract":"Perfluorooctane sulfonate (PFOS) is a ubiquitous pollutant in global aquatic ecosystems with increasing concern for its toxicity to aquatic wildlife through inadvertent exposures. To assess the likely adverse effects of PFOS exposure on aquatic wildlife inhabiting polluted ecosystems, there is a need to identify biomarkers of its exposure and toxicity. We used an integrated systems toxicological framework to identify physiologically relevant biomarkers of PFOS toxicity in fish. An in silico stoichiometric metabolism model of zebrafish (Danio rerio) was used to integrate available (published by other authors) metabolomics and transcriptomics datasets from in vivo toxicological studies with 5 days post fertilized embryo-larval life stage of zebrafish. The experimentally derived omics datasets were used as constraints to parameterize an in silico mathematical model of zebrafish metabolism. In silico simulations using flux balance analysis (FBA) and its extensions showed prominent effects of PFOS exposure on the carnitine shuttle and fatty acid oxidation. Further analysis of metabolites comprising the impacted metabolic reactions indicated carnitine to be the most highly represented cofactor metabolite. Flux simulations also showed a near dose-responsive increase in the pools for fatty acids and acyl-CoAs under PFOS exposure. Taken together, our integrative in silico results showed dyslipidemia effects under PFOS exposure and uniquely identified carnitine as a candidate metabolite biomarker. The verification of this prediction was sought in a subsequent in vivo environmental monitoring study by the authors which showed carnitine to be a modal biomarker of PFOS exposure in wild-caught fish and marine mammals sampled from the northern Gulf of Mexico. Therefore, we highlight the efficacy of FBA to study the properties of large-scale metabolic networks and to identify biomarkers of pollutant exposure in aquatic wildlife.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140376211","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

Mathematical modeling of temperature-induced circadian rhythms 温度诱导昼夜节律的数学建模

Frontiers in systems biology Pub Date : 2024-03-25 DOI: 10.3389/fsysb.2024.1256398

Lingjun Lu, Yannuo Li, Rene Schloss, Ioannis P. Androulakis

{"title":"Mathematical modeling of temperature-induced circadian rhythms","authors":"Lingjun Lu, Yannuo Li, Rene Schloss, Ioannis P. Androulakis","doi":"10.3389/fsysb.2024.1256398","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1256398","url":null,"abstract":"The central circadian pacemaker in the suprachiasmatic nuclei (SCN) aligns the phase and period of autonomous molecular oscillators in peripheral cells to daily light/dark cycles via physiological, neuronal, hormonal, and metabolic signals. Among different entrainment factors, temperature entrainment has been proposed as an essential alternative for inducing and sustaining circadian rhythms in vitro. While the synchronization mechanisms for hormones such as glucocorticoids have been widely studied, little is known about the crucial role of body temperature as a systemic cue. In this work, we develop a semi-mechanistic mathematical model describing the entrainment of peripheral clocks to temperature rhythms. The model incorporates a temperature sensing-transduction cascade involving a heat shock transcription factor-1 (HSF1) and heat shock response (HSR) pathway to simulate the entrainment of clock genes. The model is used to investigate the mammalian temperature entrainment and synchronization of cells subject to temperature oscillations of different amplitudes and magnitudes and examine the effects of transitioning between temperature schedules. Our computational analyses of the system’s dynamic responses reveal that 1) individual cells gradually synchronize to the rhythmic temperature signal by resetting their intrinsic phases to achieve coherent dynamics while oscillations are abolished in the absence of temperature rhythmicity; 2) alterations in the amplitude and period of temperature rhythms impact the peripheral synchronization behavior; 3) personalized synchronization strategies allow for differential, adaptive responses to temperature rhythms. Our results demonstrate that temperature can be a potent entrainer of circadian rhythms. Therefore, in vitro systems subjected to temperature modulation can serve as a potential tool for studying the adjustment or disruption of circadian rhythms.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140382927","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

A robust ensemble feature selection approach to prioritize genes associated with survival outcome in high-dimensional gene expression data 在高维基因表达数据中优先选择与生存结果相关基因的稳健集合特征选择方法

Frontiers in systems biology Pub Date : 2024-03-21 DOI: 10.3389/fsysb.2024.1355595

Phi Le, Xingyue Gong, Leah Ung, Hai Yang, Bridget P Keenan, Li Zhang, Tao He

{"title":"A robust ensemble feature selection approach to prioritize genes associated with survival outcome in high-dimensional gene expression data","authors":"Phi Le, Xingyue Gong, Leah Ung, Hai Yang, Bridget P Keenan, Li Zhang, Tao He","doi":"10.3389/fsysb.2024.1355595","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1355595","url":null,"abstract":"Exploring features associated with the clinical outcome of interest is a rapidly advancing area of research. However, with contemporary sequencing technologies capable of identifying over thousands of genes per sample, there is a challenge in constructing efficient prediction models that balance accuracy and resource utilization. To address this challenge, researchers have developed feature selection methods to enhance performance, reduce overfitting, and ensure resource efficiency. However, applying feature selection models to survival analysis, particularly in clinical datasets characterized by substantial censoring and limited sample sizes, introduces unique challenges. We propose a robust ensemble feature selection approach integrated with group Lasso to identify compelling features and evaluate its performance in predicting survival outcomes. Our approach consistently outperforms established models across various criteria through extensive simulations, demonstrating low false discovery rates, high sensitivity, and high stability. Furthermore, we applied the approach to a colorectal cancer dataset from The Cancer Genome Atlas, showcasing its effectiveness by generating a composite score based on the selected genes to correctly distinguish different subtypes of the patients. In summary, our proposed approach excels in selecting impactful features from high-dimensional data, yielding better outcomes compared to contemporary state-of-the-art models.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140221450","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

Calcium oscillations in HEK293 cells lacking SOCE suggest the existence of a balanced regulation of IP3 production and degradation 缺乏 SOCE 的 HEK293 细胞中的钙振荡表明 IP3 的产生和降解存在平衡调控

Frontiers in systems biology Pub Date : 2024-03-15 DOI: 10.3389/fsysb.2024.1343006

Clara Octors, Ryan E. Yoast, Scott M. Emrich, Mohamed Trebak, James Sneyd

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Computational insights in cell physiology 细胞生理学的计算见解

Frontiers in systems biology Pub Date : 2024-03-13 DOI: 10.3389/fsysb.2024.1335885

Geneviève Dupont, Didier Gonze

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Expanding our thought horizons in systems biology and medicine 拓展我们在系统生物学和医学方面的思维视野

Frontiers in systems biology Pub Date : 2024-03-06 DOI: 10.3389/fsysb.2024.1385458

Jennifer C. Lovejoy

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Pareto task inference analysis reveals cellular trade-offs in diffuse large B-Cell lymphoma transcriptomic data 帕累托任务推理分析揭示弥漫大 B 细胞淋巴瘤转录组数据中的细胞权衡问题

Frontiers in systems biology Pub Date : 2024-03-01 DOI: 10.3389/fsysb.2024.1346076

Jonatan Blais, Julie Jeukens

{"title":"Pareto task inference analysis reveals cellular trade-offs in diffuse large B-Cell lymphoma transcriptomic data","authors":"Jonatan Blais, Julie Jeukens","doi":"10.3389/fsysb.2024.1346076","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1346076","url":null,"abstract":"One of the main challenges in cancer treatment is the selection of treatment resistant clones which leads to the emergence of resistance to previously efficacious therapies. Identifying vulnerabilities in the form of cellular trade-offs constraining the phenotypic possibility space could allow to avoid the emergence of resistance by simultaneously targeting cellular processes that are involved in different alternative phenotypic strategies linked by trade-offs. The Pareto optimality theory has been proposed as a framework allowing to identify such trade-offs in biological data from its prediction that it would lead to the presence of specific geometrical patterns (polytopes) in, e.g., gene expression space, with vertices representing specialized phenotypes. We tested this approach in diffuse large B-cell lymphoma (DLCBL) transcriptomic data. As predicted, there was highly statistically significant evidence for the data forming a tetrahedron in gene expression space, defining four specialized phenotypes (archetypes). These archetypes were significantly enriched in certain biological functions, and contained genes that formed a pattern of shared and unique elements among archetypes, as expected if trade-offs between essential functions underlie the observed structure. The results can be interpreted as reflecting trade-offs between aerobic energy production and protein synthesis, and between immunotolerant and immune escape strategies. Targeting genes on both sides of these trade-offs simultaneously represent potential promising avenues for therapeutic applications.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140086210","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}

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Assessing electrogenetic activation via a network model of biological signal propagation 通过生物信号传播网络模型评估电基因激活作用

Frontiers in systems biology Pub Date : 2024-03-01 DOI: 10.3389/fsysb.2024.1291293

Kayla Chun, Eric VanArsdale, Elebeoba May, Gregory F. Payne, William E. Bentley

{"title":"Assessing electrogenetic activation via a network model of biological signal propagation","authors":"Kayla Chun, Eric VanArsdale, Elebeoba May, Gregory F. Payne, William E. Bentley","doi":"10.3389/fsysb.2024.1291293","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1291293","url":null,"abstract":"Introduction: Molecular communication is the transfer of information encoded by molecular structure and activity. We examine molecular communication within bacterial consortia as cells with diverse biosynthetic capabilities can be assembled for enhanced function. Their coordination, both in terms of engineered genetic circuits within individual cells as well as their population-scale functions, is needed to ensure robust performance. We have suggested that “electrogenetics,” the use of electronics to activate specific genetic circuits, is a means by which electronic devices can mediate molecular communication, ultimately enabling programmable control.Methods: Here, we have developed a graphical network model for dynamically assessing electronic and molecular signal propagation schemes wherein nodes represent individual cells, and their edges represent communication channels by which signaling molecules are transferred. We utilize graph properties such as edge dynamics and graph topology to interrogate the signaling dynamics of specific engineered bacterial consortia.Results: We were able to recapitulate previous experimental systems with our model. In addition, we found that networks with more distinct subpopulations (high network modularity) propagated signals more slowly than randomized networks, while strategic arrangement of subpopulations with respect to the inducer source (an electrode) can increase signal output and outperform otherwise homogeneous networks.Discussion: We developed this model to better understand our previous experimental results, but also to enable future designs wherein subpopulation composition, genetic circuits, and spatial configurations can be varied to tune performance. We suggest that this work may provide insight into the signaling which occurs in synthetically assembled systems as well as native microbial communities.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140089081","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}

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BioModels’ Model of the Year 2023 生物模型公司的 2023 年模型

Frontiers in systems biology Pub Date : 2024-02-27 DOI: 10.3389/fsysb.2024.1363884

Rahuman S. Malik Sheriff, Hiroki Asari, Henning Hermjakob, Wolfgang Huber, Thomas Quail, Silvia D. M. Santos, Amber M. Smith, Virginie Uhlmann

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