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Contribution of farms to the microbiota in the swine value chain 猪场对猪价值链中微生物群的贡献
Pub Date : 2023-07-12 DOI: 10.3389/fsysb.2023.1183868
Pascal Laforge, A. T. Vincent, C. Duchaine, Perrine Feutry, Annick Dion-Fortier, Pier-Luc Plante, Éric Pouliot, S. Fournaise, L. Saucier
Introduction: A thorough understanding of the microbial ecology within the swine value chain is essential to develop new strategies to optimize the microbiological quality of pork products. To our knowledge, no study to date has followed the microbiota through the value chain from live farm animals to the cuts of meat obtained for market. The objective of this study is to evaluate how the microbiota of pigs and their environment influence the microbial composition of samples collected throughout the value chain, including the meat plant and meat cuts.Method and results: Results from 16S rDNA sequencing, short-chain fatty acid concentrations and metabolomic analysis of pig feces revealed that the microbiota from two farms with differing sanitary statuses were distinctive. The total aerobic mesophilic bacteria and Enterobacteriaceae counts from samples collected at the meat plant after the pre-operation cleaning and disinfection steps were at or around the detection limit and the pigs from the selected farms were the first to be slaughtered on each shipment days. The bacterial counts of individual samples collected at the meat plant did not vary significantly between the farms. Alpha diversity results indicate that as we move through the steps in the value chain, there is a clear reduction in the diversity of the microbiota. A beta diversity analysis revealed a more distinct microbiota at the farms compared to the meat plant which change and became more uniform as samples were taken towards the end of the value chain. The source tracker analysis showed that only 12.92% of the microbiota in shoulder samples originated from the farms and 81% of the bacteria detected on the dressed carcasses were of unknown origin.Discussion: Overall, the results suggest that with the current level of microbial control at farms, it is possible to obtain pork products with similar microbiological quality from different farms. However, broader studies are required to determine the impact of the sanitary status of the herd on the final products.
导言:深入了解猪价值链中的微生物生态对于制定优化猪肉产品微生物质量的新策略至关重要。据我们所知,迄今为止还没有研究跟踪微生物群从活的农场动物到市场上获得的肉类的整个价值链。本研究的目的是评估猪的微生物群及其环境如何影响整个价值链中收集的样品的微生物组成,包括肉类工厂和肉类切割。方法与结果:对猪粪进行16S rDNA测序、短链脂肪酸浓度和代谢组学分析,结果表明卫生状况不同的两个猪场的微生物群存在差异。在操作前的清洁和消毒步骤后,从肉类工厂收集的样本中,有氧嗜温细菌和肠杆菌科细菌总数达到或接近检测限,并且在每个装运日,来自选定农场的猪首先被屠宰。在肉厂收集的单个样本的细菌计数在农场之间没有显着差异。α多样性结果表明,随着我们在价值链中移动的步骤,微生物群的多样性明显减少。一项beta多样性分析显示,与肉类工厂相比,农场的微生物群更加独特,随着样本走向价值链的末端,肉类工厂的微生物群会发生变化,并变得更加均匀。来源跟踪分析显示,肩部样品中仅有12.92%的微生物群来自养殖场,在屠宰后的胴体上检测到的细菌中有81%来源不明。讨论:总体而言,结果表明,以目前农场的微生物控制水平,有可能从不同的农场获得微生物质量相似的猪肉产品。但是,需要进行更广泛的研究,以确定畜群的卫生状况对最终产品的影响。
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引用次数: 0
Application of machine learning in combination with mechanistic modeling to predict plasma exposure of small molecules 机器学习与机械建模相结合的应用,以预测小分子等离子体暴露
Pub Date : 2023-06-20 DOI: 10.3389/fsysb.2023.1180948
P. D. Mavroudis, D. Teutonico, A. Abos, Nikhil Pillai
Prediction of a new molecule’s exposure in plasma is a critical first step toward understanding its efficacy/toxicity profile and concluding whether it is a possible first-in-class, best-in-class candidate. For this prediction, traditional pharmacometrics use a variety of scaling methods that are heavily based on pre-clinical pharmacokinetic (PK) data. We here propose a novel framework based on which preclinical exposure prediction is performed by applying machine learning (ML) in tandem with mechanism-based modeling. In our proposed method, a relationship is initially established between molecular structure and physicochemical (PC)/PK properties using ML, and then the ML-driven PC/PK parameters are used as input to mechanistic models that ultimately predict the plasma exposure of new candidates. To understand the feasibility of our proposed framework, we evaluated a number of mechanistic models (1-compartment, physiologically based pharmacokinetic (PBPK)), PBPK distribution models (Berezhkovskiy, PK-Sim standard, Poulin and Theil, Rodgers and Rowland, and Schmidt), and PBPK parameterizations (using in vivo, or in vitro clearance). For most of the scenarios tested, our results demonstrate that PK profiles can be adequately predicted based on the proposed framework. Our analysis further indicates some limitations when liver microsomal intrinsic clearance (CLint) is used as the only clearance pathway and underscores the necessity of investigating the variability emanating from the different distribution models when providing PK predictions. The suggested approach aims at earlier exposure prediction in the drug development process so that critical decisions on molecule screening, chemistry design, or dose selection can be made as early as possible.
预测一种新分子在血浆中的暴露是了解其功效/毒性概况并得出其是否可能是同类中第一、同类中最佳候选药物的关键的第一步。对于这种预测,传统的药物计量学使用各种各样的标度方法,这些方法在很大程度上基于临床前药代动力学(PK)数据。我们在此提出了一个新的框架,在该框架的基础上,通过将机器学习(ML)与基于机制的建模相结合来进行临床前暴露预测。在我们提出的方法中,首先使用ML建立分子结构与物理化学(PC)/PK特性之间的关系,然后将ML驱动的PC/PK参数用作机制模型的输入,最终预测新候选物的等离子体暴露。为了了解我们提出的框架的可行性,我们评估了许多机制模型(1室,基于生理的药代动力学(PBPK)), PBPK分布模型(Berezhkovskiy, PK-Sim标准,Poulin和Theil, Rodgers和Rowland,和Schmidt),以及PBPK参数化(使用体内或体外清除)。对于大多数测试场景,我们的结果表明,基于所提出的框架可以充分预测PK配置文件。我们的分析进一步表明,当肝微粒体内在清除率(CLint)被用作唯一的清除率途径时,存在一些局限性,并强调了在提供PK预测时研究不同分布模型产生的变异性的必要性。建议的方法旨在药物开发过程中的早期暴露预测,以便尽早做出分子筛选、化学设计或剂量选择的关键决策。
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引用次数: 0
A practical guide for the generation of model-based virtual clinical trials 生成基于模型的虚拟临床试验的实用指南
Pub Date : 2023-06-16 DOI: 10.3389/fsysb.2023.1174647
M. Craig, J. Gevertz, I. Kareva, K. Wilkie
Mathematical modeling has made significant contributions to drug design, development, and optimization. Virtual clinical trials that integrate mathematical models to explore patient heterogeneity and its impact on a variety of therapeutic questions have recently risen in popularity. Here, we outline best practices for creating virtual patients from mathematical models to ultimately implement and execute a virtual clinical trial. In this practical guide, we discuss and provide examples of model design, parameter estimation, parameter sensitivity, model identifiability, and virtual patient cohort creation. Our goal is to help researchers adopt these approaches to further the use of virtual population-based analysis and virtual clinical trials.
数学建模在药物设计、开发和优化方面做出了重大贡献。虚拟临床试验整合了数学模型来探索患者异质性及其对各种治疗问题的影响,最近越来越受欢迎。在这里,我们概述了从数学模型创建虚拟患者以最终实现和执行虚拟临床试验的最佳实践。在本实用指南中,我们讨论并提供了模型设计、参数估计、参数敏感性、模型可识别性和虚拟患者队列创建的示例。我们的目标是帮助研究人员采用这些方法来进一步使用基于虚拟人群的分析和虚拟临床试验。
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引用次数: 2
A computational framework for identifying chemical compounds to bind Apolipoprotein E4 for Alzheimer’s disease intervention 用于识别结合载脂蛋白E4的化合物用于阿尔茨海默病干预的计算框架
Pub Date : 2023-06-14 DOI: 10.3389/fsysb.2023.1188430
Tianhua Zhai, Emily Krass, Fangyuan Zhang, Z. Huang
Alzheimer’s disease (AD), a neurodegenerative disorder, is characterized by its ability to cause memory loss and damage other cognitive functions. Aggregation of amyloid beta (Aβ) plaques and neurofibrillary tangles in the brain are responsible for the development of Alzheimer’s disease (AD). While attempts targeting Aβ and tau proteins have been extensively conducted in the past decades, only two FDA-approved drugs (i.e., monoclonal antibodies) tackle the underlying biology of Alzheimer’s disease. In this study, an integrated computational framework was developed to identify new drug targets for Alzheimer’s disease and identify small molecules as potential therapeutical options. A systematic investigation of the gene networks firstly revealed that the Apolipoprotein E4 (ApoE4) gene plays a central role among genes associated with Alzheimer’s disease. The ApoE4 protein was then chosen as the protein target based on its role in the main pathological hallmarks of AD, which has been shown to increase Aβ accumulation by directly binding to Aβ as well as interfering with Aβ clearance that is associated with other receptors. A library of roughly 1.5 million compounds was then virtually screened via a ligand-protein docking program to identify small-molecule compounds with potential binding capacity to the ApoE4 N-terminal domain. On the basis of compound properties, 312 compounds were selected, analyzed and clustered to further identify common structures and essential functional groups that play an important role in binding ApoE4. The in silico prediction suggested that compounds with four common structures of sulfon-amine-benzene, 1,2-benzisothiazol-3-amine 1,1-dioxide, N-phenylbenzamide, and furan-amino-benzene presented strong hydrogen bonds with residues E27, W34, R38, D53, D153, or Q156 in the N terminal of ApoE4. These structures might also form strong hydrophobic interactions with residues W26, E27, L28, L30, G31, L149, and A152. While the 312 compounds can serve as drug candidates for further experiment assays, the four common structures, along with the residues for hydrogen bond or hydrophobic interaction, pave the foundation to further optimize the compounds as better binders of ApoE4.
阿尔茨海默病(AD)是一种神经退行性疾病,其特点是能够导致记忆丧失和其他认知功能受损。大脑中淀粉样蛋白β(Aβ)斑块和神经原纤维缠结的聚集是阿尔茨海默病(AD)发展的原因。尽管在过去几十年中,针对Aβ和tau蛋白的尝试已经广泛进行,但只有两种美国食品药品监督管理局批准的药物(即单克隆抗体)能够解决阿尔茨海默病的潜在生物学问题。在这项研究中,开发了一个集成的计算框架,以确定阿尔茨海默病的新药靶点,并确定小分子作为潜在的治疗选择。对基因网络的系统研究首次揭示了载脂蛋白E4(ApoE4)基因在阿尔茨海默病相关基因中起着核心作用。然后,根据ApoE4蛋白在AD的主要病理特征中的作用,选择ApoE4蛋白质作为蛋白质靶点,该蛋白已被证明通过直接与Aβ结合以及干扰与其他受体相关的Aβ清除来增加Aβ的积累。然后通过配体-蛋白质对接程序对大约150万种化合物的文库进行了虚拟筛选,以鉴定具有与ApoE4 N-末端结构域潜在结合能力的小分子化合物。在化合物性质的基础上,对312个化合物进行了筛选、分析和聚类,以进一步鉴定在结合ApoE4中起重要作用的常见结构和必需官能团。计算机预测表明,具有四种常见结构的化合物,即亚砜胺苯、1,2-苯并异噻唑-3-胺1,1-二氧化物、N-苯基苯甲酰胺和呋喃氨基苯,在ApoE4的N末端与残基E27、W34、R38、D53、D153或Q156形成强氢键。这些结构也可能与残基W26、E27、L28、L30、G31、L149和A152形成强疏水相互作用。虽然312种化合物可以作为进一步实验测定的候选药物,但四种常见结构,以及氢键或疏水相互作用的残基,为进一步优化化合物作为ApoE4的更好粘合剂奠定了基础。
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引用次数: 0
Single-cell technologies for multimodal omics measurements 用于多模式组学测量的单细胞技术
Pub Date : 2023-04-21 DOI: 10.3389/fsysb.2023.1155990
Dongsheng Bai, Chenxu Zhu
The recent surge in single-cell genomics, including the development of a wide range of experimental and computational approaches, has provided insights into the complex molecular networks of cells during development and in human diseases at unprecedented resolution. Single-cell transcriptome analysis has enabled high-resolution investigation of cellular heterogeneity in a wide range of cell populations ranging from early embryos to complex tissues—while posing the risk of only capturing a partial picture of the cells’ complex molecular networks. Single-cell multiomics technologies aim to bridge this gap by providing a more holistic view of the cell by simultaneously measuring multiple molecular types from the same cell and providing a more complete view of the interactions and combined functions of multiple regulatory layers at cell-type resolution. In this review, we briefly summarized the recent advances in multimodal single-cell technologies and discussed the challenges and opportunities of the field.
最近单细胞基因组学的激增,包括各种实验和计算方法的发展,以前所未有的分辨率提供了对发育过程中细胞复杂分子网络和人类疾病的见解。单细胞转录组分析使得从早期胚胎到复杂组织的大范围细胞群体的细胞异质性的高分辨率研究成为可能,同时也带来了仅捕获细胞复杂分子网络的部分图像的风险。单细胞多组学技术旨在通过同时测量来自同一细胞的多种分子类型,提供更全面的细胞视图,并在细胞类型分辨率上提供更完整的相互作用和多个调节层的组合功能视图,从而弥合这一差距。在这篇综述中,我们简要总结了多式联运单电池技术的最新进展,并讨论了该领域的挑战和机遇。
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引用次数: 0
An approach to learn regulation to maximize growth and entropy production rates in metabolism 一种学习调节的方法,以最大限度地提高新陈代谢的生长和熵产率
Pub Date : 2023-04-05 DOI: 10.3389/fsysb.2023.981866
Ethan King, Jesse T. Holzer, J. North, W. Cannon
Elucidating cell regulation remains a challenging task due to the complexity of metabolism and the difficulty of experimental measurements. Here we present a method for prediction of cell regulation to maximize cell growth rate while maintaining the solvent capacity of the cell. Prediction is formulated as an optimization problem using a thermodynamic framework that can leverage experimental data. We develop a formulation and variable initialization procedure that allows for computing solutions of the optimization with an interior point method. The approach is applied to photoheterotrophic growth of Rhodospirilium rubrum using ethanol as a carbon source, which has applications to biosynthesis of ethylene production. Growth is captured as the rate of synthesis of amino acids into proteins, and synthesis of nucleotide triphoshaptes into RNA and DNA. The method predicts regulation that produces a high rate of protein and RNA synthesis while DNA synthesis is reduced close to zero in agreement with production of DNA being turned off for much of the cell cycle.
由于代谢的复杂性和实验测量的难度,阐明细胞调控仍然是一项具有挑战性的任务。在这里,我们提出了一种预测细胞调节的方法,以最大限度地提高细胞的生长速度,同时保持细胞的溶剂容量。预测是制定为一个优化问题,使用热力学框架,可以利用实验数据。我们开发了一个公式和变量初始化过程,允许用内点法计算优化的解。该方法应用于以乙醇为碳源的红红螺旋藻的光异养生长,在乙烯生产的生物合成中具有应用价值。生长被捕获为氨基酸合成蛋白质的速率,以及核苷酸三磷酸体合成RNA和DNA的速率。该方法预测了产生高蛋白质和RNA合成率的调节,而DNA合成减少到接近于零,这与DNA生产在细胞周期的大部分时间被关闭一致。
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引用次数: 0
Editorial: Education in systems biology 2022 社论:系统生物学教育2022
Pub Date : 2023-03-13 DOI: 10.3389/fsysb.2023.1176588
E. Saccenti
The launch of the Research Topic dedicated to Education in Systems Biology 2022 (https://www.frontiersin.org/research-topics/28852/education-in-systems-biology2022#overview) originated from the recognition by the Editorial Board of Frontiers in Systems Biology of the crucial role that education at the graduate and post-graduate level can play in fostering systems thinking through the use of mathematical reasoning and modeling. This Research Topic aimed to emphasize the importance of educating and training students from both biological and mathematical backgrounds in how to think in a systematic way to address modern biological and biomedical problems. We invited manuscripts that address questions such as effective methods for teaching math and computation applied to biological systems, available software tools for teaching systems biology research, best practices for teaching students with different backgrounds, core concepts of systems science and how these concepts can be taught, and fundamental mathematical tools required for systems reasoning. This Research Topic was also aimed at offering the possibility of publication and research credits for teaching efforts, which are an integral (and often very relevant) part of the activity of academic researchers but are often not acknowledged due to the lack of appropriate journals dedicated to education. The Research Topic “Education in Systems Biology 2022” published four articles: three were dedicated to teaching strategies and course development in systems biology, while the fourth addressed, from a didactical point, the fundamental problem of parameter estimation. The article “Research-driven education: An introductory course to systems and synthetic biology” by Smith et al., presents an approach to teaching systems and synthetic biology to undergraduate students based on the DBTL (Design-Build-Test-Learn) framework. It introduces a course designed to provide students with hands-on experience in conducting research in these fields as well as to introduce them to the latest tools and technologies used in these areas. The course presented is structured around a research project in which students work in teams to design and execute experiments, analyze data, and present their findings. The authors highlight the benefits of this approach, including the development of critical thinking skills, the promotion of scientific communication, and the enhancement of scientific literacy. The article provides an overview of the course structure, including the learning objectives, the research project covered, and the assessment methods used. The authors also discuss the challenges and opportunities associated with implementing this approach, OPEN ACCESS
2022年系统生物学教育研究主题的启动(https://www.frontiersin.org/research-topics/28852/education-in-systems-biology2022#overview)起源于《系统生物学前沿》编辑委员会对研究生和研究生教育通过数学推理和建模在培养系统思维方面发挥的关键作用的认识。本研究主题旨在强调教育和培训具有生物学和数学背景的学生如何以系统的方式思考现代生物学和生物医学问题的重要性。我们邀请了一些手稿,这些手稿涉及的问题包括:应用于生物系统的数学和计算教学的有效方法、用于教学系统生物学研究的可用软件工具、教授不同背景学生的最佳实践、系统科学的核心概念以及如何教授这些概念,以及系统推理所需的基本数学工具。这一研究主题还旨在为教学工作提供出版和研究学分的可能性,这是学术研究人员活动的一个组成部分(通常非常相关),但由于缺乏专门用于教育的适当期刊,往往得不到承认。研究主题“2022年系统生物学教育”发表了四篇文章:其中三篇致力于系统生物学的教学策略和课程开发,而第四篇则从教学角度探讨了参数估计的基本问题。Smith等人的文章《研究驱动的教育:系统和合成生物学入门课程》提出了一种基于DBTL(设计-构建-测试-学习)框架向本科生教授系统和合成生物的方法。它介绍了一门课程,旨在为学生提供在这些领域进行研究的实践经验,并向他们介绍在这些领域使用的最新工具和技术。本课程围绕一个研究项目展开,学生们组队设计和执行实验,分析数据,并展示他们的发现。作者强调了这种方法的好处,包括培养批判性思维技能、促进科学交流和提高科学素养。本文概述了课程结构,包括学习目标、涵盖的研究项目和使用的评估方法。作者还讨论了与实施这种方法“开放访问”相关的挑战和机遇
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引用次数: 0
Mapping out the gut microbiota-dependent trimethylamine N-oxide super pathway for systems biology applications 为系统生物学应用绘制肠道微生物群依赖性三甲胺氮氧化物超级途径
Pub Date : 2023-03-08 DOI: 10.3389/fsysb.2023.1074749
Isabel M. E. Valenbreder, S. Balăn, M. Breuer, M. Adriaens
The metabolic axis linking the gut microbiome and heart is increasingly being researched in the context of cardiovascular health. The gut microbiota-derived trimethylamine/trimethylamine N-oxide (TMA/TMAO) pathway is responsible along this axis for the bioconversion of dietary precursors into TMA/TMAO and has been implicated in the progression of heart failure and dysbiosis through a positive-feedback interaction. Systems biology approaches in the context of researching this interaction offer an additional dimension for deepening the understanding of metabolism along the gut-heart axis. For instance, genome-scale metabolic models allow to study the functional role of pathways of interest in the context of an entire cellular or even whole-body metabolic network. In this mini review, we provide an overview of the latest findings on the TMA/TMAO super pathway and summarize the current state of knowledge in a curated pathway map on the community platform WikiPathways. The pathway map can serve both as a starting point for continual curation by the community as well as a resource for systems biology modeling studies. This has many applications, including addressing remaining gaps in our understanding of the gut-heart axis. We discuss how the curated pathway can inform a further curation and implementation of the pathway in existing whole-body metabolic models, which will allow researchers to computationally simulate this pathway to further understand its role in cardiovascular metabolism.
在心血管健康的背景下,连接肠道微生物群和心脏的代谢轴越来越多地被研究。肠道微生物来源的三甲胺/三甲胺n -氧化物(TMA/TMAO)途径沿着这条轴负责将饮食前体生物转化为TMA/TMAO,并通过正反馈相互作用与心力衰竭和生态失调的进展有关。在研究这种相互作用的背景下,系统生物学方法为深化对肠-心轴代谢的理解提供了一个额外的维度。例如,基因组尺度的代谢模型允许在整个细胞甚至全身代谢网络的背景下研究感兴趣的途径的功能作用。在这篇小型综述中,我们概述了TMA/TMAO超级通路的最新发现,并总结了社区平台WikiPathways上策划的通路图中的当前知识状态。路径图既可以作为社区持续管理的起点,也可以作为系统生物学建模研究的资源。这有很多应用,包括解决我们对肠心轴的理解中的空白。我们讨论了如何在现有的全身代谢模型中进一步管理和实施这一途径,这将使研究人员能够计算模拟这一途径,以进一步了解其在心血管代谢中的作用。
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引用次数: 0
Network motifs and hypermotifs in TGFβ-induced epithelial to mesenchymal transition and metastasis tgf β诱导的上皮向间质过渡和转移中的网络基序和高基序
Pub Date : 2023-03-03 DOI: 10.3389/fsysb.2023.1099951
Gottumukkala Sai Bhavani, A. Palanisamy
Epithelial to mesenchymal transition (EMT) is a complex, non-linear, dynamic multistep process that plays an integral role in the development of metastatic cancers. A diverse range of signaling molecules, along with their associated pathways, were observed to be involved in promoting EMT and cancer metastasis. Transforming growth factor–β (TGFβ), through its SMAD-dependent and SMAD-independent signaling, orchestrates numerous regulators that converge on key EMT transcription factors (TFs). These TFs further govern the phenotypic transition of cancer cells from epithelial to mesenchymal states. This study explores the TGFβ signaling pathway and its unique network architecture to understand their information processing roles in EMT. Two coherent type 1 feed forward network motifs regulating the expression of SNAIL and N-cadherin were observed. SNAIL, which is one of the crucial regulators of EMT, links both the coherent type 1 feed forward loops (C1FFLs) leading to hypermotif-like structure (Adler and Medzhitov, 2022). Systems modeling and analysis of these motifs and hypermotifs illustrated several interesting emergent information processing roles of the regulators involved. The known roles of these regulators, as described in the literature, were highly correlated with the emergent properties observed. The motifs illustrated persistence detection and noise filtration in regulating the expression of SNAIL and N-cadherin. Along with these system-level properties, the hypermotif architecture also exhibited temporal expression of GLI, SNAIL, ZEB, and N-cadherin. Furthermore, a hypothetical three-layered C1FFL hypermotif was postulated and analyzed. The analysis revealed various interesting system-level properties. However, possible existence of such real biological networks needs further exploration both theoretically and experimentally. Deciphering these network motifs and hypermotifs has provided an additional understanding of the complex biological phenomenon, such as EMT in cancer metastasis.
上皮-间充质转化(EMT)是一个复杂、非线性、动态的多步骤过程,在转移性癌症的发展中起着不可或缺的作用。观察到多种信号分子及其相关途径参与促进EMT和癌症转移。转化生长因子-β(TGFβ)通过其SMAD依赖性和SMAD非依赖性信号传导,协调了许多聚集在关键EMT转录因子(TF)上的调节因子。这些TF进一步控制癌症细胞从上皮状态向间充质状态的表型转变。本研究探讨了TGFβ信号通路及其独特的网络结构,以了解其在EMT中的信息处理作用。观察到两个连贯的1型前馈网络基序调节SNAIL和N-钙粘蛋白的表达。SNAIL是EMT的关键调节因子之一,它将导致超基序样结构的相干1型前馈环(C1FFL)连接起来(Adler和Medzhitov,2022)。对这些基序和超基序的系统建模和分析说明了所涉及的调节因子的几个有趣的突发信息处理作用。正如文献中所描述的,这些调节因子的已知作用与观察到的涌现特性高度相关。这些基序说明了在调节SNAIL和N-钙粘蛋白表达中的持久性检测和噪声过滤。除了这些系统级特性外,超基序结构还表现出GLI、SNAIL、ZEB和N-钙粘蛋白的时间表达。此外,假设并分析了一个假设的三层C1FFL超基序。分析揭示了各种有趣的系统级特性。然而,这种真实的生物网络的可能存在需要进一步的理论和实验探索。解码这些网络基序和超基序提供了对复杂生物现象的额外理解,例如癌症转移中的EMT。
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引用次数: 0
Changes in multimorbidity burden over a 3–5 year period among people with HIV HIV感染者3-5年多发病负担的变化
Pub Date : 2023-02-27 DOI: 10.3389/fsysb.2023.1136999
Luxsena Sukumaran, D. De Francesco, A. Winston, P. Mallon, N. Doyle, Jane Anderson, M. Boffito, I. Williams, F. Post, J. Vera, M. Sachikonye, Margaret A. Johnson, C. Sabin
Introduction: As people living with HIV age, the increasing burden of multimorbidity poses a significant health challenge. The aims of this study were to identify common patterns of multimorbidity and examine changes in their burden, as well as their associations with risk factors, over a 3–5 year period in people with HIV, enrolled in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study. Methods: Common multimorbidity patterns were identified in POPPY participants with HIV using principal component analysis, based on Somers’ D statistic. Multimorbidity burden scores were calculated for each participant/pattern at study entry/follow-up and were standardised relative to the mean in the sample at baseline (scores >0 thus reflect a greater number of comorbidities relative to the mean). Two multivariable linear regression models were fitted to examine the associations between risk factors and burden z-scores at baseline and change in z-scores over a 3–5 year period. Results: Five patterns were identified among the 1073 POPPY participants with HIV {median age [interquartile range (IQR)], 52 (47–59) years; 85% male and 84% white}: Cardiovascular diseases (CVDs), Sexually transmitted diseases (STDs), Neurometabolic, Cancer and Mental-gastro-joint. The multivariable linear regression showed that older age, behavioural factors (i.e., body mass index (BMI), history of injection drug use, current recreational drug use and sex between men), and HIV-specific factors (i.e., duration since HIV diagnosis and a prior AIDS diagnosis) were associated with higher multimorbidity burden at baseline. However, only three of the factors (age, BMI and duration since HIV diagnosis) were significantly associated with an increase in burden across specific patterns over time. Discussion: Key modifiable and non-modifiable factors contributing to an increase in burden of multimorbidity were identified. Our findings may inform the development of more targeted interventions and guidelines to effectively prevent and manage the rising burden of multimorbidity in people with HIV.
随着艾滋病毒感染者年龄的增长,多重疾病负担的增加对健康构成了重大挑战。本研究的目的是在参加50岁以上人群药代动力学和临床观察(POPPY)研究的HIV感染者中,确定多发病的常见模式,并检查其负担的变化及其与风险因素的关联。方法:采用基于Somers ' D统计量的主成分分析,确定罂粟参与者中常见的多发病模式。在研究开始/随访时计算每个参与者/模式的多重疾病负担评分,并相对于基线时样本的平均值进行标准化(因此评分>0反映了相对于平均值更多的合并症)。我们拟合了两个多变量线性回归模型,以检验危险因素与基线时的负担z分数以及3-5年期间z分数变化之间的关系。结果:在1073名HIV感染者中发现了五种模式{中位年龄[四分位数间距(IQR)], 52(47-59)岁;85%为男性,84%为白人}:心血管疾病(cvd)、性传播疾病(std)、神经代谢疾病、癌症和精神-胃关节疾病。多变量线性回归显示,年龄较大、行为因素(即身体质量指数(BMI)、注射吸毒史、目前使用娱乐性药物和男性之间的性行为)和艾滋病毒特异性因素(即自艾滋病毒诊断和既往艾滋病诊断的持续时间)与基线时较高的多重疾病负担相关。然而,随着时间的推移,只有三个因素(年龄、体重指数和自艾滋病毒诊断以来的持续时间)与特定模式的负担增加显著相关。讨论:确定了导致多重疾病负担增加的关键可改变和不可改变因素。我们的研究结果可能为制定更有针对性的干预措施和指南提供信息,以有效预防和管理艾滋病毒感染者多重疾病日益增加的负担。
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Frontiers in systems biology
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