Systems biology
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[[Image:Genomics GTL Pictorial Program.jpg|thumb|320px|Example of systems biology research.]]
'''Systems biology''' is a relatively new biological study field that focuses on the systematic study of complex interactions in [[biological system| biological systems]], thus using a new perspective (integration instead of [[reductionist|reduction]]) to study them. Particularly from year 2000 onwards, the term is used widely in the [[biosciences]], and in a variety of contexts. Because the scientific method has been used primarily toward reductionism, one of the goals of systems biology is to discover new emergent properties that may arise from the systemic view used by this discipline in order to understand better the entirety of processes that happen in a biological system.
== Overview ==
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]]).<ref name = "defandperspectives">{{cite conference | last = Snoep J.L. and Westerhoff H.V. | coauthors = Alberghina L. and Westerhoff H.V. (Eds.)| title = From isolation to integration, a systems biology approach for building the Silicon Cell | booktitle = Systems Biology: Definitions and Perspectives | publisher = Springer-Verlag | date = 2005. | pages = p7}}</ref><ref name = "isbdef">{{cite web | url = http://www.systemsbiology.org/Intro_to_ISB_and_Systems_Biology/Systems_Biology_--_the_21st_Century_Science | title = Systems Biology - the 21st Century Science }}</ref>
* 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 quantitative measures, multiple components simultaneously and by rigorous data integration with mathematical models"'' [[Science (journal)|Science]]<ref>{{cite journal | author=Sauer, U. et al.| title=Getting Closer to the Whole Picture | journal=Science| volume=316| pages= 550| date=17 April 2007 | pmid = 17463274 | doi = 10.1126/science.1142502 }}</ref>
:''"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]]<ref>{{cite book| author=[[Denis Noble]] | title=The Music of Life: Biology beyond the genome | publisher= Oxford University Press| year=2006| isbn=978-0199295739}} p21</ref>
*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.<ref name="bbsrc">{{cite web | url = http://www.bbsrc.ac.uk/science/areas/ebs/themes/main_sysbio.html | title = Systems Biology: Modelling, Simulation and Experimental Validation }}</ref>.<ref name="quant">{{cite conference | last = Kholodenko B.N., Bruggeman F.J., Sauro H.M. | coauthors = Alberghina L. and Westerhoff H.V.(Eds.)| title = Mechanistic and modular approaches to modeling and inference of cellular regulatory networks | booktitle = Systems Biology: Definitions and Perspectives | publisher = Springer-Verlag | date = 2005. | pages = p143}}</ref> 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.<!-- sourced below.-->
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.
==History==
Systems biology finds its roots in:
*the quantitative modelling of [[enzyme kinetics]], a discipline that flourished between [[1900]] and [[1970]],
*the simulations developed to study neurophysiology, and
*[[control theory]], and [[cybernetics]].
One of the theorists who can be seen as a precursor of systems biology is [[Ludwig von Bertalanffy]] with his [[general systems theory]]. One of the first numerical simulations in 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.<ref>{{cite journal | author=Hodgkin AL, Huxley AF | year=1952 | title= A quantitative description of membrane current and its application to conduction and excitation in nerve |journal=J Physiol | volume=117 | pages=500–544 | pmid = 12991237 }}</ref> Their model described a cellular function emerging from the interaction between two different molecular components, a potassium and a sodium channels, and can therefore be seen as the beginning of computational systems biology.<ref>{{cite journal| author=Le Novere | year=2007 | title= The long journey to a Systems Biology of neuronal function | journal=BMC Systems Biology| volume=1 |pages= 28 | doi= 10.1186/1752-0509-1-28}}</ref> In 1960, [[Denis Noble]] developed the first computer model of the heart pacemaker.<ref>{{cite journal| author=Noble D | year=1960 | title= Cardiac action and pacemaker potentials based on the Hodgkin-Huxley equations | journal=Nature | volume= 188 | pages= 495–497 | pmid=13729365 | doi= 10.1038/188495b0}}</ref>
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."<ref>{{cite book | last = Mesarovic | first = M. D. | authorlink = Mihajlo Mesarovic | title = Systems Theory and Biology | publisher = [[Springer-Verlag]] | year = 1968 }}</ref><ref>{{cite journal |title= A Means Toward a New Holism |journal= Science |volume= 161 |issue= 3836|pages=34-35 |url=http://www.jstor.org/view/00368075/ap004022/00a00220/0 | doi = 10.1126/science.161.3836.34 }}</ref>
The [[1960]]s and [[1970]]s 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 [[1980]]s, 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.
However the birth of [[functional genomics]] in the [[1990]]s 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.
Around the year [[2000]], when Institutes 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<ref name="careers">{{cite web
| url = http://sciencecareers.sciencemag.org/career_development/previous_issues/articles/2006_03_03/working_the_systems/(parent)/158
| title = Working the Systems }}</ref> several doctoral training centres in systems biology have been established in many parts of the world.
== Techniques associated with systems biology ==
[[Image:Signal transduction v1.png|280px|thumb|right|Overview of [[signal transduction]] pathways]]
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:
* [[Transcriptomics]]: whole cell or tissue gene expression measurements by [[DNA microarray]]s or [[serial analysis of gene expression]]
* [[Proteomics]]: complete identification of proteins and protein expression patterns of a cell or tissue through [[two-dimensional gel electrophoresis]] and [[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]]: identification and measurement of all small-molecules [[metabolites]] within a cell or tissue
* [[Glycomics]]: identification of the entirety of all carbohydrates in a cell or tissue.
In addition to the identification and quantification of the above given molecules further techniques analyze the dynamics and interactions within a cell. This includes:
* [[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
* [[Biomics]]: systems analysis of the [[biome]].
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.
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.<ref>{{cite journal | last=Gardner | first=TS | coauthors=di Bernardo D, Lorenz D and Collins JJ | date=04 Jul 2003 | title=Inferring genetic networks and identifying compound of action via expression profiling
| journal=Science | volume=301 | pages=102-1005 | pmid=12843395 | doi = 10.1126/science.1081900 }}</ref><ref>{{cite journal | last=di Bernardo | first=D | coauthors=Thompson MJ, Gardner TS, Chobot SE, Eastwood EL, Wojtovich AP, Elliot SJ, Schaus SE and Collins JJ | date=Mar 2005 | title=Chemogenomic profiling on a genome-wide scale using reverse-engineered gene networks
| journal=Nature Biotechnology | volume=23 | pages=377-383 | pmid=15765094 | doi = 10.1038/nbt1075 }}</ref> 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]]), approaches to database integration and software interoperability via loose coupling of software, websites and databases <ref>(such as Gaggle [http://gaggle.systemsbiology.net], or SBW [http://sys-bio.org]),</ref> and the development of syntactically and semantically sound ways of representing biological models, such as the [[Systems Biology Markup Language]].
== See also ==
{{multicol}}
;Related fields
*[[Biological systems engineering]]
*[[Biomedical cybernetics]]
*[[Biostatistics]]
*[[Computational Biology]]
*[[Computational systems biology]]
*[[Living systems theory]]
*[[Metabolic network modelling]]
*[[Scotobiology]]
*[[Synthetic biology]]
*[[Systems ecology]]
*[[Systems immunology]]
*[[Systems theory]]
{{multicol-break}}
;Related terms
*[[Artificial life]]
*[[Autopoiesis]]
*[[Computer simulation]]
*[[Gene regulatory network]]
*[[List of omics topics in biology]]
*[[List of publications in biology#Systems biology|List of publications in systems biology]]
*[[List of systems biology research groups]]
*[[Model (abstract)|Model]]
*[[Network Theory of Aging]]
*[[Regulome]]
*[[Systems Biology Markup Language]]
*[[SBO]]
*[[Viable System Model]]
{{multicol-break}}
;Systems biologists
* [[:Category:Systems biologists]]
* [[Alan Aderem]]
* [[Ruedi Aebersold]]
* [[Søren Brunak]]
* [[Guido Caldarelli]]
* [[George Church]]
* [[James Collins (Boston University)|James Collins]]
* [[Pardis Sabeti]]
* [[Joost Schymkowitz]]
* [[Pamela Silver]]
{{multicol-end}}
== Bibliography ==
=== Books ===
* H Kitano (editor). ''Foundations of Systems Biology.'' MIT Press: 2001. ISBN 0-262-11266-3
* 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
* E Klipp, R Herwig, A Kowald, C Wierling, and H Lehrach. ''Systems Biology in Practice.'' Wiley-VCH: 2005. ISBN 3-527-31078-9
* L. Alberghina and H. Westerhoff (Editors) – ''Systems Biology: Definitions and Perspectives'', Topics in Current Genetics 13, Springer Verlag (2005), ISBN 13: 978-3540229681
* A Kriete, R Eils. ''Computational Systems Biology.'', Elsevier - Academic Press: 2005. ISBN 0-12-088786-X
* K. Sneppen and G. Zocchi, (2005) ''Physics in Molecular Biology'', [[Cambridge University Press]], ISBN 0-521-84419-3
* D. Noble, [http://www.musicoflife.co.uk/ ''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
* B Palsson, [http://gcrg.ucsd.edu/book/index.html ''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
* U Alon. ''An Introduction to Systems Biology: Design Principles of Biological Circuits.'' CRC Press: 2006. ISBN 1-58488-642-0 - emphasis on Network Biology (For a comparative review of Alon, Kaneko and Palsson see<ref name="Review">{{cite journal | author=Werner, E. | url = http://www.nature.com/nature/journal/v446/n7135/pdf/446493a.pdf
| title = All systems go| journal= Nature| volume=446 |pages=493-494 | date= March 29, 2007 | doi = 10.1038/446493a }} </ref> )
=== Articles ===
* M. Tomita, 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. [http://web.sfc.keio.ac.jp/~mt/mt-lab/publications/Paper/ecell/bioinfo99/btc007_gml.html]
* [http://www.sciencemag.org/content/vol295/issue5560/ ScienceMag.org] - Special Issue: Systems Biology, ''[[Science (journal)|Science]]'', Vol 295, No 5560, March 1, 2002
* Marc Vidal and Eileen E. M. Furlong. Nature Reviews Genetics 2004 [http://www.nature.com/nrg/journal/v5/n10/poster/omics/index.html From OMICS to systems biology]
* Marc Facciotti, Richard Bonneau, Leroy Hood and Nitin Baliga. Current Genomics 2004 [http://www.ingentaconnect.com/content/ben/cg/2004/00000005/00000007/art00002 Systems Biology Experimental Design - Considerations for Building Predictive Gene Regulatory Network Models for Prokaryotic Systems]
* Katia Basso, Adam A Margolin, Gustavo Stolovitzky, Ulf Klein, Riccardo Dalla-Favera, Andrea Califano, (2005) [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15778709&query_hl=7 "Reverse engineering of regulatory networks in human B cells"]. Nat Genet;37(4):382-90
* Mario Jardon [http://www.scq.ubc.ca/?p=253 Systems Biology: An Overview] - a review from the Science Creative Quarterly, 2005
* Johnjoe McFadden, [http://www.guardian.co.uk/life/science/story/0,12996,1477776,00.html 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', ''[[The Guardian]]'' (May 6, 2005)
* Pharoah, M.C. (online). [http://homepage.ntlworld.com/m.pharoah/ Looking to systems theory for a reductive explanation of phenomenal experience and evolutionary foundations for higher order thought] Retrieved Jan, 15 2008.
* WTEC Panel Report on [http://www.wtec.org/sysbio/welcome.htm International Research and Development in Systems Biology] (2005)
* E. Werner, "The Future and Limits of Systems Biology", [http://stke.sciencemag.org/content/vol2005/issue278/ Science STKE] 2005, pe16 (2005).
* Francis J. Doyle and Jörg Stelling, [http://www.journals.royalsoc.ac.uk/openurl.asp?genre=article&doi=10.1098/rsif.2006.0143 "Systems interface biology"] ''J. R. Soc. Interface'' Vol 3, No 10 2006
* Kahlem, P. and Birney E. (2006). "Dry work in a wet world: computation in systems biology." [http://www.nature.com/doifinder/10.1038/msb4100080 Mol Syst Biol 2: 40.]
* E. Werner, [http://www.nature.com/nature/journal/v446/n7135/pdf/446493a.pdf "All systems go"], [http://www.nature.com/nature/journal/v446/n7135/index.html "Nature"] vol 446, pp 493-494, March 29, 2007. (Review of three books (Alon, Kaneko, and Palsson) on systems biology.)
* Santiago Schnell, Ramon Grima, Philip K. Maini, [http://www.americanscientist.org/template/AssetDetail/assetid/54784 "Multiscale Modeling in Biology"], American Scientist, Vol 95, pages 134-142, March-April 2007.
* TS Gardner, D di Bernardo, D Lorenz and JJ Collins. [http://www.bu.edu/abl/publications.html "Inferring genetic networks and identifying compound of action via expression profiling."] Science 301: 102-105 (2003).
* Jeffery C. Way and Pamela A. Silver, [http://cs.calstatela.edu/wiki/images/9/9b/Silver.pdf Why We Need Systems Biology]
* H.S. Wiley, "Systems Biology - Beyond the Buzz." [http://www.the-scientist.com/2006/6/1/52/1/ The Scientist]. June 2006.]
* Nina Flanagan, [http://www.genengnews.com/articles/chitem.aspx?aid=2337 "Systems Biology Alters Drug Development."] Genetic Engineering & Biotechnology News, January 2008
== References ==
{{reflist}}
== External links ==
{{Commonscat|Systems biology}}
{{Wiktionary}}
<!-- Please use the talk page to propose any additions to this section. Feel free to add research groups and labs to the List_of_Systems_Biology_Research_Groups article -->
* [http://www.nature.com/msb Molecular Systems Biology] - open access journal on systems biology
* [http://www.biomedcentral.com/bmcsystbiol BMC Systems Biology] - open access journal on systems biology
* [http://www.ietdl.org/IET-SYB IET Systems Biology] - not open access journal on systems biology
* [http://mips.gsf.de/proj/biorel/ BIOREL resource for quantitative estimation of the gene network bias in relation to available database information]
* [http://www.biochemweb.org/systems.shtml Systems Biology - BioChemWeb.org]
* [http://www.systems-biology.org/ Systems Biology Portal] - administered by the Systems Biology Institute
* [http://www.systems-biology.com/ Applied Industrial Systems Biology] - administered by the Competence Center Systems Biology of Bayer Technology Services GmbH
* [http://www.systembiologie.de/en/index.html Systems Biology Portal of Germany] - administered by HepatoSys, the German competence network for Systems Biology of liver cells
* [http://www.systemsx.ch/ Swiss Initiative in Systems Biology]
* [http://www.mathworks.com/company/newsletters/news_notes/june07/simbiology.html Studying the World's Most Complex Dynamic Systems] By Ricardo Paxson and Kristen Zannell, The MathWorks website.
* [http://www2.warwick.ac.uk/fac/sci/sbdtc/ Warwick University Systems Biology Doctoral Training Centre] - offering EPSRC grants for select individuals to study Systems Biology at MSc and then PhD level.
* [http://www.bu.edu/abl Systems Biology at Boston University]
* [http://www.sbi.uni-rostock.de Systems Biology and Bioinformatics at Rostock University, Germany]
*[http://www.sysbio.org Systems Biology at Pacific Northwest National Laboratory]
* [http://www.basysbio.eu/ BaSysBio (Bacillus Systems Biology)] - European integrated project on Bacillus Systems Biology
* [http://www.icr.ac.uk/research/research_sections/cell_and_molecular_biology/cell_and_mol_biology_teams/network_syst_biology/index.shtml Systems & Network Biology at ICR, London, UK.]
* [http://www.abdn.ac.uk/sysbio Systems Biology Masters Programme at the University of Aberdeen, Scotland, UK.]
* [http://www.sbtoolbox2.org/ Systems Biology Toolbox 2 for MATLAB]: User-friendly MATLAB toolbox for modeling, simulation, and analysis of biochemical systems. Includes powerful simulation and parameter estimation methods.
* [http://www.potterswheel.de/ PottersWheel: Systems Biology Multi-Experiment Fitting MATLAB Toolbox]
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