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Molecularbiologyhasuntilnowmainlyfocussedonindividualmolecules,on theirpropertiesasisolatedentitiesorascomplexesinverysimplemodelsystems. However,biologicalmoleculesinlivingsystemsparticipateinverycomplexn- works,includingregulatorynetworksforgeneexpression,intracellularmetabolic networksandbothintra-andintercellularcommunicationnetworks. Suchn- worksareinvolvedinthemaintenance(homeostasis)aswellasthedi?erentiation ofcellularsystemsofwhichwehaveaveryincompleteunderstanding. Nevertheless,theprogressinmolecularbiologyhasmadepossiblethedetailed descriptionofthecomponentsthatconstitutelivingsystems,notablygenesand proteins. Large-scalegenomesequencingmeansthatwecan(atleastinpr- ciple)delineateallmacromolecularcomponentsofagivencellularsystem,and microarrayexperimentsaswellaslarge-scaleproteomicswillsoongiveuslarge amountsofexperimentaldataongeneregulation,molecularinteractionsand cellularnetworks. Thechallengeofthe21stcenturywillbetounderstandhow theseindividualcomponentsintegrateintocomplexsystemsandthefunction andevolutionofthesesystems,thusscalingupfrommolecularbiologytos- temsbiology. Bycombiningexperimentaldatawithadvancedformaltheories fromcomputerscience, theformallanguageforbiologicalsystems tospecify dynamicmodelsofinteractingmolecularentitieswouldbeessentialfor:(i)- derstandingthenormalbehaviourofcellularprocesses,andhowchangesmay a?ecttheprocessesandcausedisease itmaybepossibletocorrelategenetic propertiesandsymptomsinnewandmoree?cientways,basedonanactual- derstandingofhowvariousprocessesinteract;(ii)providingpredictabilityand ?exibilitytoacademic,pharmaceutical,biotechnologyandmedicalresearchers studyinggeneorproteinfunctions. Inparticular,itmaysavetimebyreducing thenumberofexperimentsneeded,ifinadequatehypothesescanbeexcludedby computersimulation. Inresponsetothecallforpapers39weresubmittedtoCMSB2003. Allthe submittedpaperswerereviewedandtheprogrammecommittee(listedbelow) selected11high-qualitypapersforpublicationinthisvolume. Thecareofthe reviewersandoftheprogrammecommitteemembersinreviewingthepapers wassurelyvaluable. Afurther11paperswereselectedonlyforpresentationat theworkshopinordertostimulatediscussions(anabstractisincluded). AttheworkshopEhudShapiroandMichaelSterngavetwoinvited talks whosetopicsaredescribedinpapersincludedinthisvolume. Theprogramme committeedecidedtoacceptforpublicationinthisvolumealsosomeposition papers that highlight the research trends in this new ?eld of computational methodsinsystemsbiology. Thereasonisthatbecausethisisthe?rstedition ofaworkshopinthisfast-growing?eldalargeviewofpotentialtopicsofresearch wasconsideredextremelyimportant. Rovereto,December2002 CorradoPriami ProgrammeCommitteeofCMSB 2003 CorradoPriami(Chair),UniversityofTrento(Italy), CharlesAu?ray,CNRS,Villejuif(France), CosimaBaldari,UniversitadiSiena(Italy), AlexanderBockmayr,Universit eHenriPoincar e(France), LucaCardelli,MicrosoftResearchCambridge(UK), VincentDanos,Universit eParisVII(France), PierpaoloDegano,Universitad
iPisa(Italy), Francois Fages,INRIA,Rocquencourt(France), DrabløsFinn,NorwegianUniversityofScienceandTechnology,Trondheim(N- way), MonikaHeiner,BrandenburgUniversityofTechnologyatCottbus(Germany), InaKoch,UniversityofAppliedSciencesBerlin,(Germany), JohnE. Ladbury,UniversityCollegeLondon(UK), PatrickLincoln,SRI(USA), SatoruMiyano,UniversityofTokyo(Japan), GordonPlotkin,UniversityofEdinburgh(UK), SimonPlyte,PharmaciaCorporation(Italy), AvivRegev,WeizmannInstituteofScience(Israel), MagaliRoux-Rouqui e,BSMIPasteurInstitute(France), VincentSchachter,HybrigenicsParis(France), MasaruTomita,KeioUniversity(Japan), AdelindeUhrmacher,UniversityofRostock(Germany), AlfonsoValencia,CNB-CSIC,CentroNacionaldeBiotecnologia(Spain), OlafWolkenhauer,UMIST,Manchester(UK) Local Organizing Committee Corrado Priami, Linda Brodo, Michela de Concini, Debora Schuch da Rosa Machado,andtheUniversityofTrentoEventsandMeetingsO?ce. List ofReferees F. Abascal,N. Chabrier,A. Cimatti,M. Curti,M. D. Devignes,S. Gnesi, J. Guijarro,K.
Includes supplementary material: sn.pub/extras
Inhalt
Invited Papers.- Cells as Computation.- Formal Modeling of C. elegans Development: A Scenario-Based Approach.- Regular Papers.- Causal ?-Calculus for Biochemical Modelling.- Graphs for Core Molecular Biology.- Contribution of Computational Tree Logic to Biological Regulatory Networks: Example from Pseudomonas Aeruginosa.- Modeling Cellular Behavior with Hybrid Automata: Bisimulation and Collapsing.- Multiscale Modeling of Alternative Splicing Regulation.- A Method for Estimating Metabolic Fluxes from Incomplete Isotopomer Information.- Dynamic Bayesian Network and Nonparametric Regression for Nonlinear Modeling of Gene Networks from Time Series Gene Expression Data.- Discrete Event Simulation for a Better Understanding of Metabolite Channeling - A System Theoretic Approach.- Mathematical Modeling of the Influence of RKIP on the ERK Signaling Pathway.- A Method to Identify Essential Enzymes in the Metabolism: Application to Escherichia Coli.- Symbolic Model Checking of Biochemical Networks.- Presentation Abstracts.- Coupled Oscillator Models for a Set of Communicating Cells.- Representing and Simulating Protein Functional Domains in Signal Transduction Using Maude.- A Core Modeling Language for the Working Molecular Biologist (Abstract).- Integrating Simulation Packages via Systems Biology Mark-Up Language.- Recreating Biopathway Databases towards Simulation.- How to Synthesize an Optimized Genetic ?-Switching System? A System-Theoretic Approach Based on SQP.- Simulation Sudy of the TNF? Mediated NF-?B Signaling Pathway.- Detection and Analysis of Unexpected State Components in Biological Systems.- Model Validation of Biological Pathways Using Petri Nets - Demonstrated for Apoptosis.- An Overview of Data Models for the Analysis of Biochemical Pathways.- DiscreteEvent Systems and Client-Server Model for Signaling Mechanisms.- Position Papers.- Enhanced Operational Semantics in Systems Biology.- Issues in Computational Methods for Functional Genomics and Systems Biology.- Integrating Biological Process Modelling with Gene Expression Data and Ontologies for Functional Genomics (Position Paper).- Computer Simulation of Protocells.- How to Solve Semantic Puzzles of Systems Biology.- Evolution as Design Engineer.- Inference, Modeling and Simulation of Gene Networks.