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Encyclopedia > Systems biology

Systems biology is a term used very widely in the biosciences, particularly from the year 2000 onwards, and in a variety of contexts. Systems biology can be considered from a number of different aspects:

  • Some sources discuss systems biology 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)[1][2].
  • Other sources consider systems biology as a paradigm, usually defined in antithesis to the so-called reductionist paradigm, 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 quantitiative measures, multiple components simultaneously and by rigorous data integration with mathematical models" Science[3] Neuraminidase ribbon diagram An enzyme (in Greek en = in and zyme = blend) is a protein, or protein complex, that catalyzes a chemical reaction and also controls the 3D orientation of the catalyzed substrates. ... Metabolites are the intermediates and products of metabolism. ... In biochemistry, a metabolic pathway is a series of chemical reactions occurring within a cell, catalyzed by enzymes, resulting in either the formation of a metabolic product to be used or stored by the cell, or the initiation of another metabolic pathway (then called a flux generating step). ... Since the late 1960s, the word paradigm (IPA: ) has referred to a thought pattern in any scientific discipline or other epistemological context. ... Reductionism in philosophy describes a number of related, contentious theories that hold, very roughly, that the nature of complex things can always be reduced to (explained by) simpler or more fundamental things. ... Scientific method is a body of techniques for investigating phenomena and acquiring new knowledge, as well as for correcting and integrating previous knowledge. ... Science is the journal of the American Association for the Advancement of Science (AAAS). ...

"Systems 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 Noble[4] This article or section does not cite its references or sources. ...

  • Still other sources view systems biology in terms of the operational protocols used for performing research, namely a cycle composed of theory, 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.[5][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.
  • Finally, some sources see it 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 and institutes of systems biology proliferating worldwide. The Transcriptome is the set of all mRNA molecules (or transcripts) in one or a population of biological cells for a given set of environmental circumstances. ... Metabolomics is the systematic study of the unique chemical fingerprints that specific cellular processes leave behind - specifically, the study of their small-molecule metabolite profiles. ... This article or section is in need of attention from an expert on the subject. ... 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ...

Contents

History

Systems Biology finds its roots in quantitative modelling of enzyme kinetics, a discipline that flourished between 1900 and 1970, but also in the simulations developed to study neurophysiology, and the control theory, or cybernetics. One of the theorists who can be seen as a precursor of systems biology is Ludwig von Bertalanffy with his general systems theory. In 1952, the British neurophysiologists and nobel prize winners Alan Lloyd Hodgkin and Andrew Fielding Huxley constructed a mathematical model explaining the action potential propagating along the axon of a neuronal cell. In 1960, Denis Noble developed the first computer model of a beating heart. The years 60s and 70s view 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 80s, coupled with a skepticism toward theoretical biology, that then promised more than it achieved, caused the quantitative modelling of biological processes to become a somehow minor field. However the birth of functional genomics in the 90s meant that large quantity of good quality data became available, while the computing power exploded, making possible more realistic models. In 1997, the group of Masaru Tomita published the first quantitative model of the metabolism of a whole (hypothetical) cell. Around the year 2000, when Institute of Systems Biology were established in Seattle and Tokyo, Systems Biology emerged as a movement in its own right, spurred 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. As of summer 2006, due to a shortage of people in systems biology[7] several doctoral training centres in systems biology have been established in many parts of the world. Dihydrofolate reductase from with its two substrates, dihydrofolate (right) and NADPH (left), bound in the active site. ... Cybernetics is the study of feedback and derived concepts such as communication and control in living organisms, machines and organisations. ... Karl Ludwig von Bertalanffy (September 19, 1901, Vienna, Austria - June 12, 1972, New York, USA) was a biologist who was a founder of general systems theory--which he literally translated from the mathematization of Nicolai Hartmanns Ontology as stated by himself in his seminal work-- .An Austrian citizen, he... Systems theory or general systems theory or systemics is an interdisciplinary field which studies systems as a whole. ... Alan Lloyd Hodgkin photo: taken 1963 Nobel prize photo Sir Alan Lloyd Hodgkin, OM, KBE, FRS (February 5, 1914 – December 20, 1998) was a British physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine for his work with Andrew Fielding Huxley on the basis of nerve... Sir Andrew Fielding Huxley OM FRS (born 22 November 1917, Hampstead, London, England, UK) is a British physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine for his work with Alan Lloyd Hodgkin on the basis of nerve action potentials, the electrical impulses that enable the... This article or section does not cite its references or sources. ... Metabolic control analysis is a computational method for analysing variation in fluxes and intermediate concentrations in a metabolic pathway relating to the effects of the different enzymes that constitute the pathway. ... The Biochemical Systems Theory is a mathematical modelling framework for biochemical systems, based on ordinary differential equations (ODE), in which biochemical processes are represented using power-law expansions in the variables of the system. ... Molecular biology is the study of biology at a molecular level. ... Theoretical biology is an interdisciplinary field of academic study and research that involves the use of quantitative tools in biology. ... Genome projects are scientific endeavours that aim to map the genome of a living being or of a species (be it an animal, a plant, a fungus, a bacterium, an archaean, a protist or a virus), that is, the complete set of genes caried by this living being or virus. ... Informally, an omics is a neologism referring to a field of study in biology, ending in the suffix -omics such as genomics or proteomics. ... Genomics is the study of an organisms entire genome. ... This article or section is in need of attention from an expert on the subject. ... Map of the human X chromosome (from the NCBI website). ...


Techniques associated with systems biology

According to the interpretation of System Biology as the ability to obtain, integrate and analyze complex data from multiple experimental sources using interdisciplinary tools, some typical technology platforms are:

In addition to the identification and quantification of the above given molecules further techniques analyze the dynamics and interactions within a cell. This includes: The Transcriptome is the set of all mRNA molecules (or transcripts) in one or a population of biological cells for a given set of environmental circumstances. ... It has been suggested that Gene chip technology be merged into this article or section. ... Serial analysis of gene expression (SAGE) is a technique used by molecular biologists to produce a snapshot of the messenger RNA population in a sample of interest. ... This article or section is in need of attention from an expert on the subject. ... Two-dimensional gel electrophoresis, commonly abbreviated as 2-DE or 2-D electrophoresis, is a form of gel electrophoresis commonly used to analyze proteins. ... Mass spectrometry (also known as mass spectroscopy (deprecated)[1] or informally, mass-spec and MS) is an analytical technique used to measure the mass-to-charge ratio of ions. ... Phosphoproteomics is a branch of proteomics that identifies, catalogs, and characterizes proteins containing phosphate as a post-translational modification. ... Glycoproteomics is a branch of proteomics that identifies, catalogs, and characterizes proteins containing carbohydrates as a post-translational modification. ... Metabolomics is the systematic study of the unique chemical fingerprints that specific cellular processes leave behind - specifically, the study of their small-molecule metabolite profiles. ... Metabolites are the intermediates and products of metabolism. ... Glycomics, or glycobiology is a discipline of biology that deals with the structure and function of oligosaccharides (chains of sugars). ...

  • Interactomics which is used mostly in the context of protein-protein interaction but in theory encompasses interactions between all molecules within a cell
  • Fluxomics, which deals with the dynamic changes of molecules within a cell over time

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. 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. 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. Systems biology is an academic field that seeks to integrate biological data as an attempt to understand how biological systems function. ... In molecular biology, RNA interference (RNAi) is a mechanism in which the presence of small fragments of double-stranded RNA (dsRNA) whose sequence matches a given gene interferes with the expression of that gene. ...


The investigations of a single level of biological organization (such as those listed above) are usually referred to as Systematic Systems Biology. Other areas of Systems Biology includes Integrative Systems Biology, which seeks to integrate different types of information to advance the understanding the biological whole, and Dynamic Systems Biology, which aims to uncover how the biological whole changes over time (during evolution, for example, the onset of disease or in response to a perturbation). Functional Genomics may also be considered a sub-field of Systems Biology.


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. For instance, a cellular network can be modelled mathematically using methods coming from chemical kinetics and control theory. Due to the large number of parameters, variables and constraints in cellular networks, numerical and computational techniques are often used. Other aspects of computer science and informatics are also used in systems biology. These include new forms of computational model, such as the use of process calculi to model biological processes, the integration of information from the literature, using techniques of information extraction and text mining, the development of online databases and repositories for sharing data and models (such as BioModels Database), and the development of syntactically and semantically sound ways of representing biological models, such as the Systems Biology Markup Language. The process calculi (or process algebras) are a diverse family of related approaches to formally modelling concurrent systems. ... Information extraction (IE) is a type of information retrieval whose goal is to automatically extract structured or semistructured information from unstructured machine-readable documents. ... Text mining, sometimes alternately referred to as text data mining, refers generally to the process of deriving high quality information from text. ... BioModels Database is a free and open-source database for storing, exchanging and retrieving published quantitative models of biological interest. ... The Systems Biology Markup Language (SBML) is a machine-readable language, derived from XML, for representing models of biochemical reaction networks. ...


Bibliography

Books

  • U Alon. An Introduction to Systems Biology: Design Principles of Biological Circuits. CRC Press: 2006. ISBN 1-58488-642-0 - emphasis on Network Biology
  • B Palsson. Systems Biology - Properties of Reconstructed Networks. Cambridge University Press: 2006. ISBN 978-0-521-85903-5
  • K Kaneko. Life: An Introduction to Complex Systems Biology. Springer: 2006. ISBN: 3540326669
  • D Noble. The Music of life. Biology beyond the genome Oxford University Press 2006. ISBN-10: 0199295735, ISBN-13: 978-0199295739
  • Z. Szallasi, J. Stelling, and V.Periwal (eds.) System Modeling in Cellular Biology: From Concepts to Nuts and Bolts (Hardcover), MIT Press: 2006, ISBN 0-262-19548-8
  • K. Sneppen and G. Zocchi, (2005) Physics in Molecular Biology, Cambridge University Press, ISBN 0-521-84419-3
  • L. Alberghina and H. Westerhoff (Editors) – Systems Biology: Definitions and Perspectives, Topics in Current Genetics 13, Springer Verlag (2005),ISBN 13: 978-3540229681
  • E Klipp, R Herwig, A Kowald, C Wierling, and H Lehrach. Systems Biology in Practice. Wiley-VCH: 2005. ISBN 3-527-31078-9
  • A Kriete, R Eils. Computational Systems Biology., Elsevier - Academic Press: 2005. ISBN 0-12-088786-X
  • CP Fall, E Marland, J Wagner and JJ Tyson (Editors). "Computational Cell Biology." Springer Verlag: 2002 ISBN 0-387-95369-8
  • G Bock and JA Goode (eds).In Silico" Simulation of Biological Processes, Novartis Foundation Symposium 247. John Wiley & Sons: 2002. ISBN 0-470-84480-9
  • H Kitano (editor). Foundations of Systems Biology. MIT Press: 2001. ISBN 0-262-11266-3

(For a comparative review of Alon, Kaneko and Palsson see[8] ) The headquarters of the Cambridge University Press, in Trumpington Street, Cambridge. ...


Articles

  • Santiago Schnell, Ramon Grima, Philip K. Maini, "Multiscale Modeling in Biology", American Scientist, Vol 95, pages 134-142, March-April 2007.
  • Werner, E., "All systems go", "Nature" vol 446, pp 493-494, March 29, 2007. (Review of three books (Alon, Kaneko, and Palsson) on systems biology.)
  • Francis J. Doyle and Jörg Stelling, "Systems interface biology" J. R. Soc. Interface Vol 3, No 10 2006
  • Katia Basso, Adam A Margolin, Gustavo Stolovitzky, Ulf Klein, Riccardo Dalla-Favera, Andrea Califano, (2005) "Reverse engineering of regulatory networks in human B cells". Nat Genet;37(4):382-90
  • Werner, E., "The Future and Limits of Systems Biology", Science STKE 2005, pe16 (2005).
  • Guardian.co.uk - 'The unselfish gene: The new biology is reasserting the primacy of the whole organism - the individual - over the behaviour of isolated genes', Johnjoe McFadden, The Guardian (May 6, 2005)
  • [1] Assessment of International Research and Development in Systems Biology (2005)
  • Marc Facciotti, Richard Bonneau, Leroy Hood and Nitin Baliga. Current Genomics 2004 Systems Biology Experimental Design - Considerations for Building Predictive Gene Regulatory Network Models for Prokaryotic Systems
  • Marc Vidal and Eileen E. M. Furlong. Nature Reviews Genetics 2004 From OMICS to systems biology
  • ScienceMag.org - Special Issue: Systems Biology, Science, Vol 295, No 5560, March 1, 2002
  • Tomita M, Hashimoto K, Takahashi K, Shimizu T, Matsuzaki Y, Miyoshi F, Saito K, Tanida S, Yugi K, Venter JC, Hutchison CA. E-CELL: Software Environment for Whole Cell Simulation. Genome Inform Ser Workshop Genome Inform. 1997;8:147-155. [2]
  • Mario Jardon Systems Biology: An Overview - a review from the Science Creative Quarterly, 2005

The Guardian is a British newspaper owned by the Guardian Media Group. ... Science is the journal of the American Association for the Advancement of Science (AAAS). ...

External links

  • Molecular Systems Biology - open access journal on systems biology
  • BMC Systems Biology - open access journal on systems biology
  • IET Systems Biology - not open access journal on systems biology
  • BIOREL resource for quantitative estimation of the gene network bias in relation to available database information

Nickname: Motto: Sic Itur Ad Astra (Thus do we reach the stars) Location in the Commonwealth of Virginia Coordinates: Country United States State Virginia County Independent City Government  - Mayor L. Douglas Wilder (I) Area  - City 62. ... Virginia Commonwealth University, or VCU, is a large public American research university with its main campuses located in downtown Richmond, Virginia. ...

See also

The Systems Biology Markup Language (SBML) is a machine-readable language, derived from XML, for representing models of biochemical reaction networks. ... Biostatistics or biometry is the application of statistics to a wide range of topics in biology. ... Computational biology is an interdisciplinary field that applies the techniques of computer science and applied mathematics to problems inspired by biology. ... Computational systems biology is the algorithm and application development arm of systems biology. ... ÎŽThis is a navigational and informational list. ... A gene regulatory network (also called a GRN or genetic regulatory network) is a collection of DNA segments in a cell which interact with each other (indirectly through their RNA and protein expression products) and with other substances in the cell, thereby governing the rates at which genes in the... There are very few or no other articles that link to this one. ... An abstract model (or conceptual model) is a theoretical construct that represents something, with a set of variables and a set of logical and quantitative relationships between them. ... The network theory of aging supports the idea that multiple connected processes contribute to the biology of aging. ... A computer simulation or a computer model is a computer program that attempts to simulate an abstract model of a particular system. ... Canada: The Institute for Biocomplexity and Informatics at the University of Calgary; The Ottawa Institute of Systems Biology; University of Torontos The Center for Cellular and Biomolecular Research and Department of Cellular and Systems Biology; France: laboratory of mitochondrial physiopathology, University of Bordeaux ; Helix project - INRIA ; Systems Biology Group... To meet Wikipedias quality standards, this article or section may require cleanup. ... Synthetic biology is a new area of research that combines science and engineering in order to design and build novel biological functions and systems. ... Systems theory is a transdisciplinary/multiperspectual scientific domain that seeks to derive and formulate those principles that are isomorphic to all fields of scientific inquiry. ... Systems Ecology is a transdiscipline which studies ecological systems, or ecosystems. ... Regulome refers to the whole set of regulation components in a cell, tissue, organ, organisms, and species. ... Biomedical cybernetics deals with investigating signal processing, decision making and control structures in living organisms. ... Artificial Life, (commonly Alife or alife) is a field of study and art form that examines systems related to life, its processes and its evolution through simulations using computer models, robotics, and biochemistry [1] (called soft, hard, and wet approaches respectively[2]). Artificial life complements traditional Biology by trying to... // Model Checking was invented independently by E. M. Clarke and E. A. Emerson, and by J. Sifakis. ...

References

  1. ^ Snoep J.L. and Westerhoff H.V.; Alberghina L. and Westerhoff H.V. (Eds.) (2005.). "From isolation to integration, a systems biology approach for building the Silicon Cell". Systems Biology: Definitions and Perspectives: p7, Springer-Verlag. 
  2. ^ Systems Biology - the 21st Century Science.
  3. ^ Sauer, U. et al. "Getting Closer to the Whole Picture" Science (journal) 316 550 17 April 2007
  4. ^ Denis Noble The Music of Life Oxford University Press (2006) p21
  5. ^ Systems Biology: Modelling, Simulation and Experimental Validation.
  6. ^ Kholodenko B.N., Bruggeman F.J., Sauro H.M.; Alberghina L. and Westerhoff H.V.(Eds.) (2005.). "Mechanistic and modular approaches to modeling and inference of cellular regulatory networks". Systems Biology: Definitions and Perspectives: p143, Springer-Verlag. 
  7. ^ Working the Systems.
  8. ^ Werner, E., "All systems go"., Naturevol 446, pp 493-494, March 29, 2007.
Genomics topics
Genome project | Paleopolyploidy | Glycomics | Human Genome Project | Proteomics
Chemogenomics | Structural genomics | Pharmacogenetics | Pharmacogenomics | Toxicogenomics
Bioinformatics | Cheminformatics | Systems biology

  Results from FactBites:
 
Systems Biology (149 words)
Systems biology is the study of biological organisms as functional systems, and is based on the premise that to understand an organism is to understand the relations and interactions that take place between its cells, proteins and genes.
It is the scientific equivalent of the expression, “the sum of all parts is still less than the whole”, and for this reason it is theoretically opposed to molecular biology.
Systems biology is a new science, one that has developed thanks to the information that the Human Genome Project’s successful completion made available.
  More results at FactBites »

 
 

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