fundamentals of systems biology from synthetic circuits to whole cell models

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Fundamentals Of Systems Biology

Author : Markus W. Covert
ISBN : 9781498728478
Genre : Technology & Engineering
File Size : 44. 32 MB
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For decades biology has focused on decoding cellular processes one gene at a time, but many of the most pressing biological questions, as well as diseases such as cancer and heart disease, are related to complex systems involving the interaction of hundreds, or even thousands, of gene products and other factors. How do we begin to understand this complexity? Fundamentals of Systems Biology: From Synthetic Circuits to Whole-cell Models introduces students to methods they can use to tackle complex systems head-on, carefully walking them through studies that comprise the foundation and frontier of systems biology. The first section of the book focuses on bringing students quickly up to speed with a variety of modeling methods in the context of a synthetic biological circuit. This innovative approach builds intuition about the strengths and weaknesses of each method and becomes critical in the book’s second half, where much more complicated network models are addressed—including transcriptional, signaling, metabolic, and even integrated multi-network models. The approach makes the work much more accessible to novices (undergraduates, medical students, and biologists new to mathematical modeling) while still having much to offer experienced modelers--whether their interests are microbes, organs, whole organisms, diseases, synthetic biology, or just about any field that investigates living systems.

A First Course In Systems Biology

Author : Eberhard Voit
ISBN : 9781351332941
Genre : Computers
File Size : 65. 88 MB
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A First Course in Systems Biology is an introduction for advanced undergraduate and graduate students to the growing field of systems biology. Its main focus is the development of computational models and their applications to diverse biological systems. The book begins with the fundamentals of modeling, then reviews features of the molecular inventories that bring biological systems to life and discusses case studies that represent some of the frontiers in systems biology and synthetic biology. In this way, it provides the reader with a comprehensive background and access to methods for executing standard systems biology tasks, understanding the modern literature, and launching into specialized courses or projects that address biological questions using theoretical and computational means. New topics in this edition include: default modules for model design, limit cycles and chaos, parameter estimation in Excel, model representations of gene regulation through transcription factors, derivation of the Michaelis-Menten rate law from the original conceptual model, different types of inhibition, hysteresis, a model of differentiation, system adaptation to persistent signals, nonlinear nullclines, PBPK models, and elementary modes. The format is a combination of instructional text and references to primary literature, complemented by sets of small-scale exercises that enable hands-on experience, and large-scale, often open-ended questions for further reflection.

Systems Biology

Author : Edda Klipp
ISBN : 9783527336364
Genre : Medical
File Size : 67. 37 MB
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This advanced textbook is tailored for an introductory course in Systems Biology and is well-suited for biologists as well as engineers and computer scientists. It comes with student-friendly reading lists and a companion website featuring a short exam prep version of the book and educational modeling programs. The text is written in an easily accessible style and includes numerous worked examples and study questions in each chapter. For this edition, a section on medical systems biology has been included.

A First Course In Systems Biology

Author : Eberhard Voit
ISBN : 9781351332934
Genre : Computers
File Size : 74. 32 MB
Format : PDF, ePub, Mobi
Download : 149
Read : 1074

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A First Course in Systems Biology is an introduction for advanced undergraduate and graduate students to the growing field of systems biology. Its main focus is the development of computational models and their applications to diverse biological systems. The book begins with the fundamentals of modeling, then reviews features of the molecular inventories that bring biological systems to life and discusses case studies that represent some of the frontiers in systems biology and synthetic biology. In this way, it provides the reader with a comprehensive background and access to methods for executing standard systems biology tasks, understanding the modern literature, and launching into specialized courses or projects that address biological questions using theoretical and computational means. New topics in this edition include: default modules for model design, limit cycles and chaos, parameter estimation in Excel, model representations of gene regulation through transcription factors, derivation of the Michaelis-Menten rate law from the original conceptual model, different types of inhibition, hysteresis, a model of differentiation, system adaptation to persistent signals, nonlinear nullclines, PBPK models, and elementary modes. The format is a combination of instructional text and references to primary literature, complemented by sets of small-scale exercises that enable hands-on experience, and large-scale, often open-ended questions for further reflection.

Systems Biology Simulation Of Dynamic Network States

Author : Bernhard Ø. Palsson
ISBN : 9781139495424
Genre : Science
File Size : 67. 40 MB
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Biophysical models have been used in biology for decades, but they have been limited in scope and size. In this book, Bernhard Ø. Palsson shows how network reconstructions that are based on genomic and bibliomic data, and take the form of established stoichiometric matrices, can be converted into dynamic models using metabolomic and fluxomic data. The Mass Action Stoichiometric Simulation (MASS) procedure can be used for any cellular process for which data is available and allows a scalable step-by-step approach to the practical construction of network models. Specifically, it can treat integrated processes that need explicit accounting of small molecules and protein, which allows simulation at the molecular level. The material has been class-tested by the author at both the undergraduate and graduate level. All computations in the text are available online in MATLAB and MATHEMATICA® workbooks, allowing hands-on practice with the material.

Theoretical And Applied Aspects Of Systems Biology

Author : Fabricio Alves Barbosa da Silva
ISBN : 9783319749747
Genre : Computers
File Size : 20. 17 MB
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This book presents the theoretical foundations of Systems Biology, as well as its application in studies on human hosts, pathogens and associated diseases. This book presents several chapters written by renowned experts in the field. Some topics discussed in depth in this book include: computational modeling of multiresistant bacteria, systems biology of cancer, systems immunology, networks in systems biology.

Model Based Hypothesis Testing In Biomedicine

Author : Rikard Johansson
ISBN : 9789176854570
Genre : Electronic books
File Size : 85. 18 MB
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The utilization of mathematical tools within biology and medicine has traditionally been less widespread compared to other hard sciences, such as physics and chemistry. However, an increased need for tools such as data processing, bioinformatics, statistics, and mathematical modeling, have emerged due to advancements during the last decades. These advancements are partly due to the development of high-throughput experimental procedures and techniques, which produce ever increasing amounts of data. For all aspects of biology and medicine, these data reveal a high level of inter-connectivity between components, which operate on many levels of control, and with multiple feedbacks both between and within each level of control. However, the availability of these large-scale data is not synonymous to a detailed mechanistic understanding of the underlying system. Rather, a mechanistic understanding is gained first when we construct a hypothesis, and test its predictions experimentally. Identifying interesting predictions that are quantitative in nature, generally requires mathematical modeling. This, in turn, requires that the studied system can be formulated into a mathematical model, such as a series of ordinary differential equations, where different hypotheses can be expressed as precise mathematical expressions that influence the output of the model. Within specific sub-domains of biology, the utilization of mathematical models have had a long tradition, such as the modeling done on electrophysiology by Hodgkin and Huxley in the 1950s. However, it is only in recent years, with the arrival of the field known as systems biology that mathematical modeling has become more commonplace. The somewhat slow adaptation of mathematical modeling in biology is partly due to historical differences in training and terminology, as well as in a lack of awareness of showcases illustrating how modeling can make a difference, or even be required, for a correct analysis of the experimental data. In this work, I provide such showcases by demonstrating the universality and applicability of mathematical modeling and hypothesis testing in three disparate biological systems. In Paper II, we demonstrate how mathematical modeling is necessary for the correct interpretation and analysis of dominant negative inhibition data in insulin signaling in primary human adipocytes. In Paper III, we use modeling to determine transport rates across the nuclear membrane in yeast cells, and we show how this technique is superior to traditional curve-fitting methods. We also demonstrate the issue of population heterogeneity and the need to account for individual differences between cells and the population at large. In Paper IV, we use mathematical modeling to reject three hypotheses concerning the phenomenon of facilitation in pyramidal nerve cells in rats and mice. We also show how one surviving hypothesis can explain all data and adequately describe independent validation data. Finally, in Paper I, we develop a method for model selection and discrimination using parametric bootstrapping and the combination of several different empirical distributions of traditional statistical tests. We show how the empirical log-likelihood ratio test is the best combination of two tests and how this can be used, not only for model selection, but also for model discrimination. In conclusion, mathematical modeling is a valuable tool for analyzing data and testing biological hypotheses, regardless of the underlying biological system. Further development of modeling methods and applications are therefore important since these will in all likelihood play a crucial role in all future aspects of biology and medicine, especially in dealing with the burden of increasing amounts of data that is made available with new experimental techniques. Användandet av matematiska verktyg har inom biologi och medicin traditionellt sett varit mindre utbredd jämfört med andra ämnen inom naturvetenskapen, såsom fysik och kemi. Ett ökat behov av verktyg som databehandling, bioinformatik, statistik och matematisk modellering har trätt fram tack vare framsteg under de senaste decennierna. Dessa framsteg är delvis ett resultat av utvecklingen av storskaliga datainsamlingstekniker. Inom alla områden av biologi och medicin så har dessa data avslöjat en hög nivå av interkonnektivitet mellan komponenter, verksamma på många kontrollnivåer och med flera återkopplingar både mellan och inom varje nivå av kontroll. Tillgång till storskaliga data är emellertid inte synonymt med en detaljerad mekanistisk förståelse för det underliggande systemet. Snarare uppnås en mekanisk förståelse först när vi bygger en hypotes vars prediktioner vi kan testa experimentellt. Att identifiera intressanta prediktioner som är av kvantitativ natur, kräver generellt sett matematisk modellering. Detta kräver i sin tur att det studerade systemet kan formuleras till en matematisk modell, såsom en serie ordinära differentialekvationer, där olika hypoteser kan uttryckas som precisa matematiska uttryck som påverkar modellens output. Inom vissa delområden av biologin har utnyttjandet av matematiska modeller haft en lång tradition, såsom den modellering gjord inom elektrofysiologi av Hodgkin och Huxley på 1950?talet. Det är emellertid just på senare år, med ankomsten av fältet systembiologi, som matematisk modellering har blivit ett vanligt inslag. Den något långsamma adapteringen av matematisk modellering inom biologi är bl.a. grundad i historiska skillnader i träning och terminologi, samt brist på medvetenhet om exempel som illustrerar hur modellering kan göra skillnad och faktiskt ofta är ett krav för en korrekt analys av experimentella data. I detta arbete tillhandahåller jag sådana exempel och demonstrerar den matematiska modelleringens och hypotestestningens allmängiltighet och tillämpbarhet i tre olika biologiska system. I Arbete II visar vi hur matematisk modellering är nödvändig för en korrekt tolkning och analys av dominant-negativ-inhiberingsdata vid insulinsignalering i primära humana adipocyter. I Arbete III använder vi modellering för att bestämma transporthastigheter över cellkärnmembranet i jästceller, och vi visar hur denna teknik är överlägsen traditionella kurvpassningsmetoder. Vi demonstrerar också frågan om populationsheterogenitet och behovet av att ta hänsyn till individuella skillnader mellan celler och befolkningen som helhet. I Arbete IV använder vi matematisk modellering för att förkasta tre hypoteser om hur fenomenet facilitering uppstår i pyramidala nervceller hos råttor och möss. Vi visar också hur en överlevande hypotes kan beskriva all data, inklusive oberoende valideringsdata. Slutligen utvecklar vi i Arbete I en metod för modellselektion och modelldiskriminering med hjälp av parametrisk ”bootstrapping” samt kombinationen av olika empiriska fördelningar av traditionella statistiska tester. Vi visar hur det empiriska ”log-likelihood-ratio-testet” är den bästa kombinationen av två tester och hur testet är applicerbart, inte bara för modellselektion, utan också för modelldiskriminering. Sammanfattningsvis är matematisk modellering ett värdefullt verktyg för att analysera data och testa biologiska hypoteser, oavsett underliggande biologiskt system. Vidare utveckling av modelleringsmetoder och tillämpningar är därför viktigt eftersom dessa sannolikt kommer att spela en avgörande roll i framtiden för biologi och medicin, särskilt när det gäller att hantera belastningen från ökande datamängder som blir tillgänglig med nya experimentella tekniker.

Synthetic Biology

Author : Huimin Zhao
ISBN : 9780123978202
Genre : Science
File Size : 74. 44 MB
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Synthetic Biology provides a framework to examine key enabling components in the emerging area of synthetic biology. Chapters contributed by leaders in the field address tools and methodologies developed for engineering biological systems at many levels, including molecular, pathway, network, whole cell, and multi-cell levels. The book highlights exciting practical applications of synthetic biology such as microbial production of biofuels and drugs, artificial cells, synthetic viruses, and artificial photosynthesis. The roles of computers and computational design are discussed, as well as future prospects in the field, including cell-free synthetic biology and engineering synthetic ecosystems. Synthetic biology is the design and construction of new biological entities, such as enzymes, genetic circuits, and cells, or the redesign of existing biological systems. It builds on the advances in molecular, cell, and systems biology and seeks to transform biology in the same way that synthesis transformed chemistry and integrated circuit design transformed computing. The element that distinguishes synthetic biology from traditional molecular and cellular biology is the focus on the design and construction of core components that can be modeled, understood, and tuned to meet specific performance criteria and the assembly of these smaller parts and devices into larger integrated systems that solve specific biotechnology problems. Includes contributions from leaders in the field presents examples of ambitious synthetic biology efforts including creation of artificial cells from scratch, cell-free synthesis of chemicals, fuels, and proteins, engineering of artificial photosynthesis for biofuels production, and creation of unnatural living organisms Describes the latest state-of-the-art tools developed for low-cost synthesis of ever-increasing sizes of DNA and efficient modification of proteins, pathways, and genomes Highlights key technologies for analyzing biological systems at the genomic, proteomic, and metabolomic levels which are especially valuable in pathway, whole cell, and multi-cell applications Details mathematical modeling tools and computational tools which can dramatically increase the speed of the design process as well as reduce the cost of development.

Mathematical Modeling In Systems Biology

Author : Brian P. Ingalls
ISBN : 9780262018883
Genre : Science
File Size : 86. 86 MB
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Systems techniques are integral to current research in molecular cell biology, and system-level investigations are often accompanied by mathematical models. These models serve as working hypotheses: they help us to understand and predict the behavior of complex systems. This book offers an introduction to mathematical concepts and techniques needed for the construction and interpretation of models in molecular systems biology. It is accessible to upper-level undergraduate or graduate students in life science or engineering who have some familiarity with calculus, and will be a useful reference for researchers at all levels. The first four chapters cover the basics of mathematical modeling in molecular systems biology. The last four chapters address specific biological domains, treating modeling of metabolic networks, of signal transduction pathways, of gene regulatory networks, and of electrophysiology and neuronal action potentials. Chapters 3--8 end with optional sections that address more specialized modeling topics. Exercises, solvable with pen-and-paper calculations, appear throughout the text to encourage interaction with the mathematical techniques. More involved end-of-chapter problem sets require computational software. Appendixes provide a review of basic concepts of molecular biology, additional mathematical background material, and tutorials for two computational software packages (XPPAUT and MATLAB) that can be used for model simulation and analysis.

Systems Biology

Author : Bernhard Palsson
ISBN : 9781107038851
Genre : Medical
File Size : 43. 71 MB
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The first comprehensive single-authored textbook on genome-scale models and the bottom-up approach to systems biology.

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