Systems biology 系统生物学.doc

Systems biologyFrom Wikipedia, the free encyclopediaSystems biology is the study of systems of biological components, which may be molecules, cells, organisms or entire species. Living systems are dynamic and complex, and their behavior may be hard to predict from the properties of individual parts. To study them, we use quantitative measurements of the behavior of groups of interacting components, systematic measurement technologies such as genomics, bioinformatics and proteomics, and mathematical and computational models to describe and predict dynamical behavior. Systems biology is a term often used to describe a number of trends in bioscience research, and a movement which draws on those trends. Proponents （支持者，倡导者）describe systems biology as a biology-based inter-disciplinary study field that focuses on complex interactions in biological systems, claiming that it uses a new perspective (holism整体论instead of reduction). Particularly from year 2000 onwards, the term is used widely in the biosciences, and in a variety of contexts. An often stated ambition of systems biology is the modeling and discovery of emergent properties, properties of a system whose theoretical description is only possible using techniques which fall under the remit（范围，职责） of systems biology. These typically involve metabolic networks or cell signaling networks1.系统生物学维基百科，自由的百科全书系统生物学是生物组分的系统，它可以是分子，细胞，器官或整个物种的研究。生活系统是动态的，复杂的，他们的行为可能很难从单个部件的性能进行预测。要研究他们，我们使用交互组件，系统的测量技术，如基因组学，生物信息学和蛋白质组学，以及数学和计算模型来描述和预测动力学行为的群体行为的定量测量。系统生物学是通常用来描述一个号码在生物科学的研究趋势的一个术语，并且吸取这些趋势的运动。支持者（支持者，倡导者）描述了系统生物学作为侧重于生物系统的复杂交互基于生物学，跨学科的研究领域，并声称它采用了全新的视角（整体论整体论，而不是减少）。尤其自2000年起，该术语广泛生物科学中的使用，并且在各种情况下。系统生物学的一个经常提到的野心是造型和紧急性的发现，一个系统的理论描述使用落在系统生物学的职权范围（范围，职责）技术下才有可能的属性。这些通常涉及代谢网络或细胞信号网络1。OverviewSystems biology can be considered from a number of different aspects: As a field of study, particularly, the study of the interactions between the components of biological systems, and how these interactions give rise to the function and behavior of that system (for example, the enzymes and metabolites in a metabolic pathway).23 As a paradigm范例, usually defined in antithesis ntss对立面to the so-called reductionist paradigm (biological organisation), although fully consistent with the scientific method. The distinction between the two paradigms is referred to in these quotations:The reductionist approach has successfully identified most of the components and many of the interactions but, unfortunately, offers no convincing concepts or methods to understand how system properties emerge.the pluralism of causes and effects in biological networks is better addressed by observing, through quantitative measures, multiple components simultaneously and by rigorous data integration with mathematical models Sauer et al4Systems biology.is about putting together rather than taking apart, integration rather than reduction. It requires that we develop ways of thinking about integration that are as rigorous as our reductionist programmes, but different.It means changing our philosophy, in the full sense of the term Denis Noble5概观系统生物学可以从许多不同的方面被认为是：作为一个研究领域，特别是，生物系统的组件，以及这些相互作用如何产生该系统的功能和行为（例如，在代谢途径中的酶和代谢物）之间的相互作用的研究。 2 3作为范例范例，通常是在对立面ntss对立面的所谓还原模式（生物组织）的定义，虽然用科学的方法完全一致。在两种模式之间的区别是指在这些语录：“该还原方法已经成功地识别大多数组件和许多相互作用的，但不幸的是，没有提供令人信服的概念或方法来了解系统性能如何.出现的原因和影响生物网络的多元化是更好的观察处理，通过定量的措施，多个组件同时并用数学模型“严格的数据集成Sauer等4“系统生物学.大约是放在一起，而不是拆开，整合而不是减少。这要求我们开发出的严谨是我们还原的程序，但不同的思考整合的方式.这意味着改变我们的理念在长期的完全意义上的“丹尼斯贵族5 As a series of operational protocols used for performing research, namely a cycle composed of theory, analytic or computational modelling to propose specific testable hypotheses about a biological system, experimental validation, and then using the newly acquired quantitative description of cells or cell processes to refine the computational model or theory.6 Since the objective is a model of the interactions in a system, the experimental techniques that most suit systems biology are those that are system-wide and attempt to be as complete as possible. Therefore, transcriptomics, metabolomics, proteomics and high-throughput techniques are used to collect quantitative data for the construction and validation of models. As the application of dynamical systems theory to molecular biology. Indeed, the focus on the dynamics of the studied systems is the main conceptual difference between systems biology and bioinformatics. As a socioscientific phenomenon defined by the strategy of pursuing integration of complex data about the interactions in biological systems from diverse experimental sources using interdisciplinary tools and personnel.This variety of viewpoints is illustrative of the fact that systems biology refers to a cluster of peripherally overlapping concepts rather than a single well-delineated field. However the term has widespread currency and popularity as of 2007, with chairs讲座 and institutes of systems biology proliferating worldwide.作为一系列用于执行研究操作协议，也就是一个周期由理论，分析或计算模型的提出有关的生物系统，实验验证特定可检验的假设，然后使用细胞或细胞过程的新获得的定量描述是为了细化计算模型或理论。6由于目的是在一个系统中的相互作用的模型中，实验技术，大部分适合的系统生物学是那些全系统和试图尽可能完全。因此，转录组，代谢组学，蛋白质组学和高通量技术用于收集模型的构建和验证定量数据。作为动力系统理论应用到分子生物学。事实上，专注于研究系统的动态特性是系统生物学和生物信息学的主要概念上的差异。作为通过追求复杂数据的整合来自与使用跨学科的工具和人员多样实验来源生物系统的相互作用的策略定义一个socioscientific现象。这个品种观点是说明性的该系统生物学指的外周重叠的概念，而不是一个单一的公划定字段集群中的事实。然而，长期具有广泛的货币和普及截至2007年，有椅子讲座和世界各地的增殖系统生物学研究与实践。HistorySystems biology finds its roots in:citation needed the quantitative modeling of enzyme kinetics, a discipline that flourished between 1900 and 1970, the mathematical modeling of population growth, the simulations developed to study neurophysiology, and control theory and cybernetics控制论.One of the theorists who can be seen as one of the precursors of systems biology is Ludwig von Bertalanffy with his general systems theory.7 One of the first numerical simulations in cell biology was published in 1952 by the British neurophysiologists and Nobel prize winners Alan Lloyd Hodgkin and Andrew Fielding Huxley, who constructed a mathematical model that explained the action potential propagating along the axon of a neuronal cell.8 Their model described a cellular function emerging from the interaction between two different molecular components, a potassium and a sodium channel, and can therefore be seen as the beginning of computational systems biology.9 In 1960, Denis Noble developed the first computer model of the heart pacemaker.10历史系统生物学发现其根源在于：引证需要酶动力学的定量模拟，即1900年和1970年间蓬勃发展的一门学科，人口增长的数学建模，模拟开发研究神经生理学和控制理论与控制论控制论。一个谁可以被看作是系统生物学的先驱之一的理论家是贝塔朗菲与他一般系统理论。7一种在细胞生物学的第一个数值模拟是由英国神经生理学家和诺贝尔奖获得者发表于1952年艾伦劳埃德霍奇和Andrew菲尔丁黎谁构成的，即沿一个神经细胞的轴突说明动作电位传播的数学模型。8他们的模型中描述的两个不同的分子组分，钾和一之间的细胞功能从相互作用新兴因此钠通道，并且可以被看作是计算系统生物学的开头。9在1960年，丹尼斯诺布尔开发的心脏起搏器的第一计算机模型10。The formal study of systems biology, as a distinct discipline, was launched by systems theorist Mihajlo Mesarovic in 1966 with an international symposium at the Case Institute of Technology in Cleveland, Ohio entitled Systems Theory and Biology.1112The 1960s and 1970s saw the development of several approaches to study complex molecular systems, such as the Metabolic Control Analysis and the biochemical systems theory. The successes of molecular biology throughout the 1980s, coupled with a skepticism toward theoretical biology, that then promised more than it achieved, caused the quantitative modelling of biological processes to become a somewhat minor field.citation neededHowever the birth of functional genomics in the 1990s meant that large quantities of high quality data became available, while the computing power exploded, making more realistic models possible. In 1997, the group of Masaru Tomita published the first quantitative model of the metabolism of a whole (hypothetical) cell.13Around the year 2000, after Institutes of Systems Biology were established in Seattle and Tokyo, systems biology emerged as a movement in its own right, spurred鞭策 on by the completion of various genome projects, the large increase in data from the omics (e.g. genomics and proteomics) and the accompanying advances in high-throughput experiments and bioinformatics. Since then, various research institutes dedicated to systems biology have been developed. For example, the NIGMS of NIH established a project grant that is currently supporting over ten Systems Biology Centers 2 in the United States. As of summer 2006, due to a shortage of people in systems biology14 several doctoral training programs in systems biology have been established in many parts of the world. In that same year, the National Science Foundation (NSF) put forward a grand challenge for systems biology in the 21st century to build a mathematical model of the whole cell.15系统生物学的正式研究，作为一个独特的学科，是由系统理论家米哈伊洛Mesarovic于1966年推出，在技术为例研究所在俄亥俄州克利夫兰市的一次国际研讨会，题为“系统理论与生物学”。11 1220世纪60年代和70年代看到的几种方法发展研究复杂分子系统，如代谢控制分析及生化系统理论。在整个80年代分子生物学，再加上对理论生物学的怀疑，那则承诺超过其取得的成就，引起了生物过程的定量模拟成为一个有点小的领域。来源请求然而，在20世纪90年代功能基因组学的诞生，意味着大量高质量的数据变得可用，而计算功率分解，使得更现实的模型可能。 1997年，该集团富田胜发表一个整体（假设）细胞代谢的第一个定量模型132000年左右，系统生物学研究所在西雅图和东京建立后，系统生物学成为在自己的权利运动的刺激下，通过各种基因组计划，大量增加从组学数据的完成鞭策着（如基因组学和蛋白质组学）和高通量实验和生物信息学的随行进展。自那时以来，致力于系统生物学各科研院所已经开发出来。例如，美国国立卫生研究院的NIGMS确定，目前支持十多个系统生物学研究中心2在美国的一个项目资助。截至2006年夏天，由于人在系统生物学短缺的系统生物学14几个博士生培养方案已确立了在世界许多地方。在同一年，美国国家科学基金会（NSF）提出了在21世纪建立了整个单元的数学模型，系统生物学盛大的挑战。15Associated disciplinesAccording to the interpretation of Systems Biology as the ability to obtain, integrate and analyze complex data sets from multiple experimental sources using interdisciplinary tools, some typical technology platforms are: Phenomics: Organismal variation in phenotype as it changes during its life span. Genomics: Organismal deoxyribonucleic acid (DNA) sequence, including intra-organisamal cell specific variation. (i.e. Telomere length variation etc.). Epigenomics / Epigenetics: Organismal and corresponding cell specific transcriptomic regulating factors not empirically coded in the genomic sequence. (i.e. DNA methylation, Histone Acetylation etc.). Transcriptomics: Organismal, tissue or whole cell gene expression measurements by DNA microarrays or serial analysis of gene expression Interferomics: Organismal, tissue, or cell level transcript correcting factors (i.e. RNA interference) Translatomics / Proteomics: Organismal, tissue, or cell level measurements of proteins and peptides via two-dimensional gel electrophoresis, mass spectrometry or multi-dimensional protein identification techniques (advanced HPLC systems coupled with mass spectrometry). Sub disciplines include phosphoproteomics, glycoproteomics and other methods to detect chemically modified proteins. Metabolomics: Organismal, tissue, or cell level measurements of all small-molecules known as metabolites. Glycomics: Organismal, tissue, or cell level measurements of carbohydrates. Lipidomics: Organismal, tissue, or cell level measurements of lipids.In addition to the identification and quantification of the above given molecules further techniques analyze the dynamics and interactions within a cell. This includes:citation needed Interactomics: Organismal, tissue, or cell level study of interactions between molecules. Currently the authoritative molecular discipline in this field of study is protein-protein interactions (PPI), although the working definition does not pre-clude inclusion of other molecular disciplines such as those defined here. NeuroElectroDynamics: Organismal, brain computing function as a dynamic system, underlying biophysical mechanisms and emerging computation by electrical interactions. Fluxomics: Organismal, tissue, or cell level measurements of molecular dynamic changes over time. Biomics: systems analysis of the biome. 生物群系相关学科根据系统生物学作为获取，整合和分析利用跨学科的工具多实验源复杂数据集的能力的解释，一些典型的技术平台是：型组学：在表型变异有机体，因为其寿命期间变化。基因组学：有机体脱氧核糖核酸（DNA）序列，包括帧内organisamal细胞特异性变异。 （即端粒长度变化等）。表观基因/表观遗传学：有机体和相应的细胞特异性转录调控因子的基因组序列没有经验编码。 （即DNA甲基化，组蛋白乙酰化等）。转录：有机体，组织或整个细胞基因表达测量由DNA微阵列或基因表达的系列分析Interferomics：有机体，组织或细胞水平转录校正因子（即RNA干扰）Translatomics /蛋白质组学：有机体，通过双向电泳，质谱或多维蛋白质鉴定技术（加上质谱先进的HPLC系统）的蛋白质和肽的组织或细胞水平测量。子学科包括磷酸化蛋白质组学，glycoproteomics等方法来检测化学修饰的蛋白质。代谢：有机体，被称为代谢物的所有的小分子的组织或细胞水平测量。糖组学：有机体，组织或细胞水平的碳水化合物测量。脂质组学：有机体，组织或细胞级脂质测量。除了上面给出的分子的鉴定和定量进一步的技术分析在小区内的动态和交互。这包括：引证需要Interactomics：有机体，组织或细胞水平上的分子之间的相互作用的研究。目前在这一研究领域权威分子纪律是蛋白质 - 蛋白质相互作用（PPI），虽然工作定义并不预先CLUDE等分子学科包括如这里定义。NeuroElectroDynamics：有机体，大脑计算功能作为动力系统，基本的生物物理机制和新兴的计算通过电相互作用。Fluxomics：有机体，随着时间的推移分子动态变化组织或细胞水平测量。Biomics：生物群落的系统分析。生物群系The investigations are frequently combined with large-scale perturbation methods, including gene-based (RNAi, mis-expression of wild type and mutant genes) and chemical approaches using small molecule libraries.citation needed Robots and automated sensors enable such large-scale experimentation and data acquisition. These technologies are still emerging and many face problems that the larger the quantity of data produced, the lower the quality.citation needed A wide variety of quantitative scientists (computational biologists, statisticians, mathematicians, computer scientists, engineers, and physicists) are working to improve the quality of these approaches and to create, refine, and retest the models to accurately reflect observations.The systems biology approach often involves the development of mechanistic models, such as the reconstruction of dynamic systems from the quantitative properties of their elementary building blocks.1617 For instance, a cellular network can be modelled mathematically using methods coming from chemical kin