Systems biology - Wikipedia

Systems biology is the computational and mathematical analysis and modeling of complex biological systems. It is a biology-based interdisciplinary field of ... Systemsbiology FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch Computationalandmathematicalmodelingofcomplexbiologicalsystems Anillustrationofthesystemsapproachtobiology Systemsbiologyisthecomputationalandmathematicalanalysisandmodelingofcomplexbiologicalsystems.Itisabiology-basedinterdisciplinaryfieldofstudythatfocusesoncomplexinteractionswithinbiologicalsystems,usingaholisticapproach(holisminsteadofthemoretraditionalreductionism)tobiologicalresearch.[1] Particularlyfromtheyear2000onwards,theconcepthasbeenusedwidelyinbiologyinavarietyofcontexts.TheHumanGenomeProjectisanexampleofappliedsystemsthinkinginbiologywhichhasledtonew,collaborativewaysofworkingonproblemsinthebiologicalfieldofgenetics.[2]Oneoftheaimsofsystemsbiologyistomodelanddiscoveremergentproperties,propertiesofcells,tissuesandorganismsfunctioningasasystemwhosetheoreticaldescriptionisonlypossibleusingtechniquesofsystemsbiology.[1][3]Thesetypicallyinvolvemetabolicnetworksorcellsignalingnetworks.[1][4] Contents 1Overview 2History 3Associateddisciplines 4Bioinformaticsanddataanalysis 5Creatingbiologicalmodels 6Seealso 7References 8Furtherreading 9Externallinks Overview[edit] Systemsbiologycanbeconsideredfromanumberofdifferentaspects. Asafieldofstudy,particularly,thestudyoftheinteractionsbetweenthecomponentsofbiologicalsystems,andhowtheseinteractionsgiverisetothefunctionandbehaviorofthatsystem(forexample,theenzymesandmetabolitesinametabolicpathwayortheheartbeats).[5][6][7] Asaparadigm,systemsbiologyisusuallydefinedinantithesistotheso-calledreductionistparadigm(biologicalorganisation),althoughitisconsistentwiththescientificmethod.Thedistinctionbetweenthetwoparadigmsisreferredtointhesequotations:"thereductionistapproachhassuccessfullyidentifiedmostofthecomponentsandmanyoftheinteractionsbut,unfortunately,offersnoconvincingconceptsormethodstounderstandhowsystempropertiesemerge ...thepluralismofcausesandeffectsinbiologicalnetworksisbetteraddressedbyobserving,throughquantitativemeasures,multiplecomponentssimultaneouslyandbyrigorousdataintegrationwithmathematicalmodels."(Saueretal.)[8]"Systemsbiology ...isaboutputtingtogetherratherthantakingapart,integrationratherthanreduction.Itrequiresthatwedevelopwaysofthinkingaboutintegrationthatareasrigorousasourreductionistprogrammes,butdifferent. ...Itmeanschangingourphilosophy,inthefullsenseoftheterm."(DenisNoble)[7] Asaseriesofoperationalprotocolsusedforperformingresearch,namelyacyclecomposedoftheory,analyticorcomputationalmodellingtoproposespecifictestablehypothesesaboutabiologicalsystem,experimentalvalidation,andthenusingthenewlyacquiredquantitativedescriptionofcellsorcellprocessestorefinethecomputationalmodelortheory.[9]Sincetheobjectiveisamodeloftheinteractionsinasystem,theexperimentaltechniquesthatmostsuitsystemsbiologyarethosethataresystem-wideandattempttobeascompleteaspossible.Therefore,transcriptomics,metabolomics,proteomicsandhigh-throughputtechniquesareusedtocollectquantitativedatafortheconstructionandvalidationofmodels.[10] Astheapplicationofdynamicalsystemstheorytomolecularbiology.Indeed,thefocusonthedynamicsofthestudiedsystemsisthemainconceptualdifferencebetweensystemsbiologyandbioinformatics.[11] Asasocioscientificphenomenondefinedbythestrategyofpursuingintegrationofcomplexdataabouttheinteractionsinbiologicalsystemsfromdiverseexperimentalsourcesusinginterdisciplinarytoolsandpersonnel.[12] History[edit] Systemsbiologywasbegunasanewfieldofsciencearound2000,whentheInstituteforSystemsBiologywasestablishedinSeattleinanefforttolure"computational"typepeoplewhoitwasfeltwerenotattractedtotheacademicsettingsoftheuniversity.Theinstitutedidnothaveacleardefinitionofwhatthefieldactuallywas:roughlybringingtogetherpeoplefromdiversefieldstousecomputerstoholisticallystudybiologyinnewways.[13]ADepartmentofSystemsBiologyatHarvardMedicalSchoolwaslaunchedin2003.[14]In2006itwaspredictedthatthebuzzgeneratedbythe"veryfashionable"newconceptwouldcauseallthemajoruniversitiestoneedasystemsbiologydepartment,thusthattherewouldbecareersavailableforgraduateswithamodicumofabilityincomputerprogrammingandbiology.[13]In2006theNationalScienceFoundationputforwardachallengetobuildamathematicalmodelofthewholecell.[citationneeded]In2012thefirstwhole-cellmodelofMycoplasmagenitaliumwasachievedbytheKarrLaboratoryattheMountSinaiSchoolofMedicineinNewYork.Thewhole-cellmodelisabletopredictviabilityofM.genitaliumcellsinresponsetogeneticmutations.[15] Anearlierprecursorofsystemsbiology,asadistinctdiscipline,mayhavebeenbysystemstheoristMihajloMesarovicin1966withaninternationalsymposiumattheCaseInstituteofTechnologyinCleveland,Ohio,titledSystemsTheoryandBiology.Mesarovicpredictedthatperhapsinthefuturetherewouldbesuchasthingas"systemsbiology".[16][17] AccordingtoRobertRoseninthe1960s,holisticbiologyhadbecomepassébytheearly20thcentury,asmoreempiricalsciencedominatedbymolecularchemistryhadbecomepopular.[17]Echoinghimfortyyearslaterin2006Klingwritesthatthesuccessofmolecularbiologythroughoutthe20thcenturyhadsuppressedholisticcomputationalmethods.[13]By2011theNationalInstitutesofHealthhadmadegrantmoneyavailabletosupportovertensystemsbiologycentersintheUnitedStates,[18]butby2012Hunterwritesthatsystemsbiologyhadnotliveduptothehype,havingpromisedmorethanitachieved,whichhadcausedittobecomeasomewhatminorfieldwithfewpracticalapplications.Nonetheless,proponentshopedthatitmightonceprovemoreusefulinthefuture.[19] Showstrendsinsystemsbiologyresearchbypresentingthenumberofarticlesoutofthetop30citedsystemsbiologypapersduringthattimewhichincludeaspecifictopic[20] AnimportantmilestoneinthedevelopmentofsystemsbiologyhasbecometheinternationalprojectPhysiome.[citationneeded] Associateddisciplines[edit] Overviewofsignaltransductionpathways Accordingtotheinterpretationofsystemsbiologyasusinglargedatasetsusinginterdisciplinarytools,atypicalapplicationismetabolomics,whichisthecompletesetofallthemetabolicproducts,metabolites,inthesystemattheorganism,cell,ortissuelevel.[21] Itemsthatmaybeacomputerdatabaseinclude:phenomics,organismalvariationinphenotypeasitchangesduringitslifespan;genomics,organismaldeoxyribonucleicacid(DNA)sequence,includingintra-organismalcellspecificvariation.(i.e.,telomerelengthvariation);epigenomics/epigenetics,organismalandcorrespondingcellspecifictranscriptomicregulatingfactorsnotempiricallycodedinthegenomicsequence.(i.e.,DNAmethylation,Histoneacetylationanddeacetylation,etc.);transcriptomics,organismal,tissueorwholecellgeneexpressionmeasurementsbyDNAmicroarraysorserialanalysisofgeneexpression;interferomics,organismal,tissue,orcell-leveltranscriptcorrectingfactors(i.e.,RNAinterference),proteomics,organismal,tissue,orcelllevelmeasurementsofproteinsandpeptidesviatwo-dimensionalgelelectrophoresis,massspectrometryormulti-dimensionalproteinidentificationtechniques(advancedHPLCsystemscoupledwithmassspectrometry).Subdisciplinesincludephosphoproteomics,glycoproteomicsandothermethodstodetectchemicallymodifiedproteins;glycomics,organismal,tissue,orcell-levelmeasurementsofcarbohydrates;lipidomics,organismal,tissue,orcelllevelmeasurementsoflipids.[citationneeded] Themolecularinteractionswithinthecellarealsostudied,thisiscalledinteractomics.[22]Adisciplineinthisfieldofstudyisprotein-proteininteractions,althoughinteractomicsincludestheinteractionsofothermolecules.[citationneeded]Neuroelectrodynamics,wherethecomputer'sorabrain'scomputingfunctionasadynamicsystemisstudiedalongwithits(bio)physicalmechanisms;[23]andfluxomics,measurementsoftheratesofmetabolicreactionsinabiologicalsystem(cell,tissue,ororganism).[21] Inapproachingasystemsbiologyproblemtherearetwomainapproaches.Thesearethetopdownandbottomupapproach.Thetopdownapproachtakesasmuchofthesystemintoaccountaspossibleandrelieslargelyonexperimentalresults.TheRNA-Seqtechniqueisanexampleofanexperimentaltopdownapproach.Conversely,thebottomupapproachisusedtocreatedetailedmodelswhilealsoincorporatingexperimentaldata.Anexampleofthebottomupapproachistheuseofcircuitmodelstodescribeasimplegenenetwork.[24] VarioustechnologiesutilizedtocapturedynamicchangesinmRNA,proteins,andpost-translationalmodifications.Mechanobiology,forcesandphysicalpropertiesatallscales,theirinterplaywithotherregulatorymechanisms;[25]biosemiotics,analysisofthesystemofsignrelationsofanorganismorotherbiosystems;Physiomics,asystematicstudyofphysiomeinbiology. Cancersystemsbiologyisanexampleofthesystemsbiologyapproach,whichcanbedistinguishedbythespecificobjectofstudy(tumorigenesisandtreatmentofcancer).Itworkswiththespecificdata(patientsamples,high-throughputdatawithparticularattentiontocharacterizingcancergenomeinpatienttumoursamples)andtools(immortalizedcancercelllines,mousemodelsoftumorigenesis,xenograftmodels,high-throughputsequencingmethods,siRNA-basedgeneknockingdownhigh-throughputscreenings,computationalmodelingoftheconsequencesofsomaticmutationsandgenomeinstability).[26]Thelong-termobjectiveofthesystemsbiologyofcancerisabilitytobetterdiagnosecancer,classifyitandbetterpredicttheoutcomeofasuggestedtreatment,whichisabasisforpersonalizedcancermedicineandvirtualcancerpatientinmoredistantprospective.Significanteffortsincomputationalsystemsbiologyofcancerhavebeenmadeincreatingrealisticmulti-scaleinsilicomodelsofvarioustumours.[27] Thesystemsbiologyapproachofteninvolvesthedevelopmentofmechanisticmodels,suchasthereconstructionofdynamicsystemsfromthequantitativepropertiesoftheirelementarybuildingblocks.[28][29][30][31]Forinstance,acellularnetworkcanbemodelledmathematicallyusingmethodscomingfromchemicalkinetics[32]andcontroltheory.Duetothelargenumberofparameters,variablesandconstraintsincellularnetworks,numericalandcomputationaltechniquesareoftenused(e.g.,fluxbalanceanalysis).[30][32] Bioinformaticsanddataanalysis[edit] Otheraspectsofcomputerscience,informatics,andstatisticsarealsousedinsystemsbiology.Theseincludenewformsofcomputationalmodels,suchastheuseofprocesscalculitomodelbiologicalprocesses(notableapproachesincludestochasticπ-calculus,BioAmbients,BetaBinders,BioPEPA,andBranecalculus)andconstraint-basedmodeling;integrationofinformationfromtheliterature,usingtechniquesofinformationextractionandtextmining;[33]developmentofonlinedatabasesandrepositoriesforsharingdataandmodels,approachestodatabaseintegrationandsoftwareinteroperabilityvialoosecouplingofsoftware,websitesanddatabases,orcommercialsuits;network-basedapproachesforanalyzinghighdimensionalgenomicdatasets.Forexample,weightedcorrelationnetworkanalysisisoftenusedforidentifyingclusters(referredtoasmodules),modelingtherelationshipbetweenclusters,calculatingfuzzymeasuresofcluster(module)membership,identifyingintramodularhubs,andforstudyingclusterpreservationinotherdatasets;pathway-basedmethodsforomicsdataanalysis,e.g.approachestoidentifyandscorepathwayswithdifferentialactivityoftheirgene,protein,ormetabolitemembers.[34]Muchoftheanalysisofgenomicdatasetsalsoincludeidentifyingcorrelations.Additionally,asmuchoftheinformationcomesfromdifferentfields,thedevelopmentofsyntacticallyandsemanticallysoundwaysofrepresentingbiologicalmodelsisneeded.[35] Creatingbiologicalmodels[edit] Asimplethreeproteinnegativefeedbackloopmodeledwithmassactionkineticdifferentialequations.EachproteininteractionisdescribedbyaMichaelis–Mentenreaction.[36] Researchersbeginbychoosingabiologicalpathwayanddiagrammingalloftheproteininteractions.Afterdeterminingalloftheinteractionsoftheproteins,massactionkineticsisutilizedtodescribethespeedofthereactionsinthesystem.Massactionkineticswillprovidedifferentialequationstomodelthebiologicalsystemasamathematicalmodelinwhichexperimentscandeterminetheparametervaluestouseinthedifferentialequations.[37]Theseparametervalueswillbethereactionratesofeachproteinsinteractioninthesystem.Thismodeldeterminesthebehaviorofcertainproteinsinbiologicalsystemsandbringnewinsighttothespecificactivitiesofindividualproteins.Sometimesitisnotpossibletogatherallreactionratesofasystem.Unknownreactionratesaredeterminedbysimulatingthemodelofknownparametersandtargetbehaviorwhichprovidespossibleparametervalues.[38][36] Theuseofconstraint-basedreconstructionandanalysis(COBRA)methodshasbecomepopularamongsystemsbiologiststosimulateandpredictthemetabolicphenotypes,usinggenome-scalemodels.Oneofthemethodsisthefluxbalanceanalysis(FBA)approach,bywhichonecanstudythebiochemicalnetworksandanalyzetheflowofmetabolitesthroughaparticularmetabolicnetwork,bymaximizingtheobjectofinterest.[39] PlotofConcentrationsvstimeforthesimplethreeproteinnegativefeedbackloop.Allparametersaresettoeither0or1forinitialconditions.Thereactionisallowedtoproceeduntilithitsequilibrium.Thisplotisofthechangeineachproteinovertime. Seealso[edit] Systemsscienceportal Biologyportal Evolutionarybiologyportal Biologicalcomputation BioSystems(journal) Computationalbiology Exposome Interactome Listofomicstopicsinbiology Metabolicnetworkmodelling Modellingbiologicalsystems Molecularpathologicalepidemiology Networkbiology Networkmedicine Noogenesis Syntheticbiology Systemsbiomedicine Systemsimmunology Systemsmedicine TIARA(database) livingsystems References[edit] ^abcTavassoly,Iman;Goldfarb,Joseph;Iyengar,Ravi(2018-10-04)."Systemsbiologyprimer:thebasicmethodsandapproaches".EssaysinBiochemistry.62(4):487–500.doi:10.1042/EBC20180003.ISSN 0071-1365.PMID 30287586.S2CID 52922135. ^Zewail,Ahmed(2008).PhysicalBiology:FromAtomstoMedicine.ImperialCollegePress.p. 339. ^Longo,Giuseppe;Montévil,Maël(2014).PerspectivesonOrganisms-Springer.LectureNotesinMorphogenesis.doi:10.1007/978-3-642-35938-5.ISBN 978-3-642-35937-8.S2CID 27653540. 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^Zou,Yawen;Laubichler,ManfredD.(2018-07-25)."Fromsystemstobiology:Acomputationalanalysisoftheresearcharticlesonsystemsbiologyfrom1992to2013".PLOSONE.13(7):e0200929.Bibcode:2018PLoSO..1300929Z.doi:10.1371/journal.pone.0200929.ISSN 1932-6203.PMC 6059489.PMID 30044828. ^abCascante,Marta;Marin,Silvia(2008-09-30)."Metabolomicsandfluxomicsapproaches".EssaysinBiochemistry.45:67–82.doi:10.1042/bse0450067.ISSN 0071-1365.PMID 18793124. ^Cusick,MichaelE.;Klitgord,Niels;Vidal,Marc;Hill,DavidE.(2005-10-15)."Interactome:gatewayintosystemsbiology".HumanMolecularGenetics.14(suppl_2):R171–R181.doi:10.1093/hmg/ddi335.ISSN 0964-6906.PMID 16162640. ^Aur,Dorian(2012)."FromNeuroelectrodynamicstoThinkingMachines".CognitiveComputation.4(1):4–12.doi:10.1007/s12559-011-9106-3.ISSN 1866-9956.S2CID 12355069. 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Furtherreading[edit] Klipp,Edda;Liebermeister,Wolfram;Wierling,Christoph;Kowald,Axel(2016).SystemsBiology-ATextbook,2ndedition.Wiley.ISBN 978-3-527-33636-4. AsfarS.Azmi,ed.(2012).SystemsBiologyinCancerResearchandDrugDiscovery.ISBN 978-94-007-4819-4. Kitano,Hiroaki(15October2001).FoundationsofSystemsBiology.MITPress.ISBN 978-0-262-11266-6. Werner,Eric(29March2007)."Allsystemsgo".Nature.446(7135):493–494.Bibcode:2007Natur.446..493W.doi:10.1038/446493a.providesacomparativereviewofthreebooks: Alon,Uri(7July2006).AnIntroductiontoSystemsBiology:DesignPrinciplesofBiologicalCircuits.Chapman&Hall.ISBN 978-1-58488-642-6. Kaneko,Kunihiko(15September2006).Life:AnIntroductiontoComplexSystemsBiology.Springer-Verlag.Bibcode:2006lics.book.....K.ISBN 978-3-540-32666-3. Palsson,BernhardO.(16January2006).SystemsBiology:PropertiesofReconstructedNetworks.CambridgeUniversityPress.ISBN 978-0-521-85903-5. WernerDubitzky;OlafWolkenhauer;HirokiYokota;Kwan-HyunCho,eds.(13August2013).EncyclopediaofSystemsBiology.Springer-Verlag.ISBN 978-1-4419-9864-4. Externallinks[edit] LookupsystemsbiologyinWiktionary,thefreedictionary. 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