Systems Biology: Constraint-Based Reconstruction and Analysis

551 Pages·2015·66.89 MB·English

by  Bernhard Ø. Palsson

Systems Biology
Constraint-basedReconstructionandAnalysis
Recent technological advances have enabled comprehensive determination of the
molecular composition of living cells. The chemical interactions between many of
these molecules are known, giving rise to genome-scale reconstructed biochemical
reaction networks underlying cellular functions. Mathematical descriptions of the
totality of these chemical interactions lead to genome-scale models that allow the
computationofphysiologicalfunctions.
Reflecting these recent developments, this textbook explains how such quanti-
tative and computable genotype–phenotype relationships are built using a genome-
wide basis of information about the gene portfolio of a target organism. It describes
howbiologicalknowledgeisassembledtoreconstructbiochemicalreactionnetworks,
theformulationofcomputationalmodelsofbiologicalfunctions,andhowthesemod-
elscanbeusedtoaddresskeybiologicalquestionsandenablepredictivebiology.
Developedthroughextensiveclassroomuse,thebookisdesignedtoprovidestu-
dentswithasolidconceptualframeworkandaninvaluablesetofmodelingtoolsand
computationalapproaches.
Detailedlectureslides,alongwithMATLABTM andMathematicaTM workbooks,
areavailablefordownloadatwww.cambridge.org/sb.
BernhardO.PalssonistheGallettiProfessorofBioengineeringandProfessorofPedi-
atricsattheUniversityofCalifornia,SanDiego.Foralmost30years,hisresearchhas
focused on the development of large-scale models of biological functions and their
use to solve basic and applied problems in the life sciences. He has authored three
previoustextbooks.

Systems Biology
Constraint-based Reconstruction and Analysis
BERNHARD O. PALSSON
DepartmentofBioengineering,
UniversityofCaliforniaatSanDiego,USA
UniversityPrintingHouse,CambridgeCB28BS,UnitedKingdom
CambridgeUniversityPressispartoftheUniversityofCambridge.
ItfurtherstheUniversity’smissionbydisseminatingknowledgeinthepursuitof
education,learningandresearchatthehighestinternationallevelsofexcellence.
www.cambridge.org
Informationonthistitle:www.cambridge.org/9781107038851
(cid:2)c B.O.Palsson2015
Thispublicationisincopyright.Subjecttostatutoryexception
andtotheprovisionsofrelevantcollectivelicensingagreements,
noreproductionofanypartmaytakeplacewithoutthewritten
permissionofCambridgeUniversityPress.
Firstpublished2015
PrintedintheUnitedStatesofAmericabySheridanBooks,Inc.
AcatalogrecordforthispublicationisavailablefromtheBritishLibrary
LibraryofCongressCataloginginPublicationdata
Palsson,Bernhard,author.
Systemsbiology:constraint-basedreconstructionandanalysis/BernhardO.Palsson.
p. ; cm.
Includesbibliographicalreferences.
ISBN978-1-107-03885-1(Hardback)
1. Title.
[DNLM: 1. Models,Biological.2. SystemsBiology.3. MetabolicNetworksand
Pathways–physiology.QU26.5]
QH508
571.7–dc23 2014031793
ISBN978-1-107-03885-1Hardback
Additionalresourcesforthispublicationatwww.cambridge.org/sb
CambridgeUniversityPresshasnoresponsibilityforthepersistenceoraccuracyof
URLsforexternalorthird-partyinternetwebsitesreferredtointhispublication,
anddoesnotguaranteethatanycontentonsuchwebsitesis,orwillremain,
accurateorappropriate.
ToSHIREENandSIRUS

Contents
Preface xv
Listofabbreviations xvii
1 Introduction 1
1.1 TheGenotype–PhenotypeRelationship 1
1.2 SomeConceptsofGenome-scaleScience 3
1.3 TheEmergenceofSystemsBiology 8
1.4 BuildingFoundations 11
1.5 AboutThisBook 12
1.6 Summary 13
PartI NetworkReconstruction 15
2 NetworkReconstruction:TheConcept 17
2.1 ManyReactionsandTheirStoichiometry 17
2.2 ReconstructingaPathway 18
2.3 Module-by-moduleReconstruction 22
2.4 ProteinsandTheirManyStates 25
2.5 CentralE.coliEnergyMetabolism 29
2.6 Genome-scaleNetworks 29
2.7 Summary 32
3 NetworkReconstruction:TheProcess 33
3.1 BuildingKnowledgeBases 33
3.2 ReconstructionisaFour-stepProcess 35
3.3 ReconstructionisIterativeandLabor-intensive 43
3.4 TheManyUsesofReconstructions 45
3.5 Summary 49
4 MetabolisminEscherichiacoli 50
4.1 SomeBasicFactsaboutE.coli 50
4.2 History 51
4.2.1 Pre-genomeerareconstructions 53
4.2.2 Genomeerareconstructions 55
4.3 ContentoftheiJO1366Reconstruction 65
4.4 FromaReconstructiontoaComputationalModel 67
4.5 ValidationofiJO1366 68
4.6 UsesoftheE.coliGEM 70
4.7 Summary 73
5 Prokaryotes 75
5.1 StateofTheField 75
viii CONTENTS
5.2 MetabolisminPathogens 78
5.3 MetabolisminBlue-GreenAlgae 80
5.4 MetabolisminMicrobialCommunities 82
5.4.1 Systemsbiologyofcommunities 85
5.4.2 Model-basedanalysisofmicrobialcommunities 86
5.5 AnEnvironmentallyImportantOrganism 88
5.5.1 Geobactersulfurreducens 88
5.5.2 Genome-scalescienceforGeobacter 90
5.6 Summary 95
6 Eukaryotes 96
6.1 MetabolisminSaccharomycescerevisiae 96
6.1.1 Reconstructionanditsuses 96
6.1.2 Community-basedreconstruction 98
6.2 MetabolisminChlamydomonasreinhardtii 101
6.2.1 Metabolicnetworkreconstruction 101
6.2.2 Descriptionofphotonusage 102
6.3 MetabolisminHomosapiens 103
6.3.1 Recon1 104
6.3.2 UsesofRecon1 106
6.3.3 Buildingmulti-cellandmulti-tissuereconstructions 108
6.3.4 MappingRecon1ontoothermammals 114
6.3.5 Recon2 114
6.4 Summary 116
7 BiochemicalReactionNetworks 117
7.1 ProteinProperties 117
7.2 StructuralBiology 119
7.3 TranscriptionandTranslation 123
7.4 IntegratingNetworkReconstructions 128
7.5 SignalingNetworks 131
7.6 Summary 133
8 MetastructuresofGenomes 134
8.1 TheConceptofaMetastructure 134
8.2 TranscriptionalRegulatoryNetworks 138
8.3 RefactoringDNAforSyntheticBiology 142
8.4 TheChallengeofPolyomicDataIntegration 144
8.5 BuildingMathematicalDescriptions 145
8.6 Summary 148
PartII MathematicalPropertiesofReconstructedNetworks 149
9 TheStoichiometricMatrix 151
9.1 TheManyAttributesofS 151
9.2 Chemistry:SasaDataMatrix 153