About the Book
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,Universit'adiSiena(Italy), AlexanderBockmayr,Universit'eHenriPoincar'e(France), LucaCardelli,MicrosoftResearchCambridge(UK), VincentDanos,Universit'eParisVII(France), PierpaoloDegano,Universitad ' iPisa(Italy), Francois , Fages,INRIA,Rocquencourt(France), DrablosFinn,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. Hafez,E. Klipp,C. Laneve,P. LopezRomero,F. Luccio, R. Marangoni,M. Padron,M. C. Pinotti,R. Rizzi,S. Tini. Acknowledgement TheworkshopwassponsoredandpartiallysupportedbytheUniversityofTrento, ComunediRovereto,APT,andtheEUprojectIST-32072-DEGAS. Table of Contents IInvitedPapers CellsasComputation...1 AmitaiRegevandEhudShapiro FormalModelingofC. elegansDevelopment:AScenario-BasedApproach ...4
Na'aman Kam,David Harel,Hillel Kugler, RamiMarelly, AmirPnueli, E. JaneAlbertHubbard, andMichael J. Stern IIRegularPapers Causal?-CalculusforBiochemicalModelling ...21 Michele Curti,Pierpaolo Degano, andCosima Tatiana Baldari GraphsforCoreMolecularBiology ...34 Vincent Danos and Cosimo Laneve ContributionofComputationalTreeLogic toBiologicalRegulatoryNetworks: ExamplefromPseudomonasAeruginosa...47 SabinePeresandJean-PaulComet ModelingCellularBehaviorwithHybridAutomata: BisimulationandCollapsing...57 Marco Antoniotti, Bhubaneswar Mishra, Carla Piazza, Alberto Policriti, andMarta Simeoni MultiscaleModelingofAlternativeSplicingRegulation...75 Damien Eveillard, Delphine Ropers,Hidde deJong,Christiane Branlant, andAlexanderBockmayr AMethodforEstimatingMetabolicFluxes fromIncompleteIsotopomerInformation...88 JuhoRousu,AriRantanen,HannuMaaheimo, Esa Pitk. anen, KatjaSaarela, andEsko Ukkonen DynamicBayesianNetworkandNonparametricRegression forNonlinearModelingofGeneNetworks fromTimeSeriesGeneExpressionData...104 SunYongKim, SeiyaImoto, andSatoru Miyano VIII Table ofContents DiscreteEventSimulationforaBetterUnderstanding ofMetaboliteChanneling-ASystemTheoreticApproach...1
14 Daniela Degenring,Mathias Rohl, .. andAdelinde M. Uhrmacher MathematicalModelingoftheIn?uenceofRKIP ontheERKSignalingPathway...127 Kwang-HyunCho, Sung-YoungShin, Hyun-WooKim,Olaf Wolkenhauer, Brian McFerran,and WalterKolch AMethodtoIdentifyEssentialEnzymesintheMetabolism: ApplicationtoEscherichia Coli...
Table of Contents:
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.
