Table Of ContentAdvances in Biochemical Engineering/Biotechnology 160
Series Editor: T. Scheper
Intawat Nookaew Editor
Network
Biology
160
Advances in Biochemical
Engineering/Biotechnology
Serieseditor
T.Scheper,Hannover,Germany
EditorialBoard
S.Belkin,Jerusalem,Israel
T.Bley,Dresden,Germany
J.Bohlmann,Vancouver,Canada
M.B.Gu,Seoul,RepublicofKorea
W.-S.Hu,Minneapolis,MN,USA
B.Mattiasson,Lund,Sweden
J.Nielsen,Gothenburg,Sweden
H.Seitz,Potsdam,Germany
R.Ulber,Kaiserslautern,Germany
A.-P.Zeng,Hamburg,Germany
J.-J.Zhong,Shanghai,China
W.Zhou,Shanghai,China
Aims and Scope
Thisbookseriesreviewscurrenttrendsinmodernbiotechnologyandbiochemical
engineering. Its aim is to cover all aspects of these interdisciplinary disciplines,
whereknowledge,methodsandexpertisearerequiredfromchemistry,biochemis-
try,microbiology,molecularbiology,chemicalengineeringandcomputerscience.
Volumesareorganizedtopicallyandprovideacomprehensivediscussionofdevel-
opments in the field over the past 3–5 years. The series also discusses new
discoveries and applications. Special volumes are dedicated to selected topics
whichfocusonnewbiotechnologicalproductsandnewprocessesfortheirsynthe-
sisandpurification.
Ingeneral, volumes are edited by well-knownguest editors. Theseries editor and
publisherwill,however,alwaysbepleasedtoreceivesuggestionsandsupplemen-
taryinformation.ManuscriptsareacceptedinEnglish.
Inreferences,AdvancesinBiochemicalEngineering/Biotechnologyisabbreviated
asAdv.Biochem.Engin./Biotechnol.andcitedasajournal.
Moreinformationaboutthisseriesathttp://www.springer.com/series/10
Intawat Nookaew
Editor
Network Biology
With contributions by
(cid:1) (cid:1) (cid:1) (cid:1)
P. Ajawatanawong Y. Akiyama S. Dahal G. Hu
(cid:1) (cid:1) (cid:1)
D. Jacobson S. Kalapanulak A. Klanchui
(cid:1) (cid:1) (cid:1) (cid:1) (cid:1)
K. Kusonmano Y. Li Y. Li Y. Matsuzaki A. Meechai
(cid:1) (cid:1) (cid:1) (cid:1)
M. Ohue G. Pavesi S. Poudel P. Prommeenate
(cid:1) (cid:1) (cid:1)
N. Raethong T. Saithong C. Thammarongtham
(cid:1) (cid:1) (cid:1)
R.A. Thompson N. Uchikoga W. Vongsangnak
(cid:1)
D.A. Weighill F. Xiao
Editor
IntawatNookaew
DepartmentofBiomedicalInformatics
CollegeofMedicine
UniversityofArkansasforMedicalScience
LittleRock,Arkansas,USA
ComputationalBiomolecularModelingandBioinformaticsGroup
ComputerScienceandMathematicsDivision
OakRidgeNationalLaboratory
OakRidge,Tennessee,USA
ISSN0724-6145 ISSN1616-8542 (electronic)
AdvancesinBiochemicalEngineering/Biotechnology
ISBN978-3-319-56459-3 ISBN978-3-319-56460-9 (eBook)
DOI10.1007/978-3-319-56460-9
LibraryofCongressControlNumber:2017938643
©SpringerInternationalPublishingAG2017
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Preface
Biologicalsystemsareextremelycomplexandcontainmillionsofmoleculeswithin
the system. The rapid development of high throughput technologies enables us to
capturethemolecularinterplaysofmoleculesinthesystemasso-called‘OMICS’
data. This leads to the need for systematic cataloguing and organization of the
enormous amount of data generated and shared within the scientific community.
Linking these molecules and evaluating their interactions following “Network
Biology” approaches enable the insightful understanding of cellular functions
from the emerging properties of the network. This special volume focuses on the
stateoftheart,currentstatus,andapplicationsofNetworkBiology.
The volume covers broad topics on network biology such as gene networks,
transcription networks, regulatory networks, protein–proteininteraction networks,
metabolic networks, and phylogenetic networks. I am very grateful to the authors
who have contributed to this special volume by sharing their experience and
expertise in the different chapters. These diverse topics should be very useful for
readerstogainanoverviewofNetworkBiology.
OakRidge,TN,USA IntawatNookaew
v
Contents
ChIP-SeqDataAnalysistoDefineTranscriptionalRegulatory
Networks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
GiulioPavesi
GeneExpressionAnalysisThroughNetworkBiology:Bioinformatics
Approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
KanthidaKusonmano
Rigid-DockingApproachestoExploreProtein–ProteinInteraction
Space. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
YuriMatsuzaki,NobuyukiUchikoga,MasahitoOhue,andYutakaAkiyama
Protein–ProteinInterfaceandDisease:PerspectivefromBiomolecular
Networks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
GuangHu,FeiXiao,YuqianLi,YuanLi,andWanwipaVongsangnak
CyanobacterialBiofuels:StrategiesandDevelopmentsonNetwork
andModeling. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
AmornpanKlanchui,NachonRaethong,PeeradaPrommeenate,
WanwipaVongsangnak,andAsawinMeechai
Genome-ScaleModelingofThermophilicMicroorganisms. . . . . . . . . . 103
SanjeevDahal,SureshPoudel,andR.AdamThompson
NetworkingOmicDatatoEnvisageSystemsBiologicalRegulation. . . . 121
SaowalakKalapanulak,TreenutSaithong,andChinaeThammarongtham
vii
viii Contents
NetworkMetamodeling:EffectofCorrelationMetricChoiceon
PhylogenomicandTranscriptomicNetworkTopology. . . . . . . . . . . . . . 143
DeborahA.WeighillandDanielJacobson
MolecularPhylogenetics:ConceptsforaNewcomer. . . . . . . . . . . . . . . 185
PravechAjawatanawong
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
AdvBiochemEngBiotechnol(2017)160:1–14
DOI:10.1007/10_2016_43
©SpringerInternationalPublishingSwitzerland2016
Publishedonline:10January2017
ChIP-Seq Data Analysis to Define
Transcriptional Regulatory Networks
GiulioPavesi
Abstract Thefirststepinthedefinitionoftranscriptionalregulatorynetworksisto
establish correct relationships between transcription factors (TFs) and their target
genes, together with the effect of their regulatory activity (activator or repressor).
Fundamental advances in this direction have been made possible by the introduc-
tion of experimental techniques such as Chromatin Immunoprecipitation, which,
coupled with next-generation sequencing technologies (ChIP-Seq), permit the
genome-wide identification of TF binding sites. This chapter provides a survey
on how data of this kind are to be processed and integrated with expression and
othertypesofdatatoinfertranscriptionalregulatoryrulesandcodes.
Keywords ChIP-Seq,RNA-Seq,Transcriptionfactors,Transcriptionregulation
Contents
1 Introduction:ChromatinImmunoprecipitationandNext-GenerationSequencing........ 2
2 FindingTranscriptionFactorBindingSites................................................. 6
3 AssociatingBindingSiteswithTargetGenes............................................... 7
4 AssessingTFActivityfromExpressionData............................................... 8
5 MiningAvailableData....................................................................... 10
6 Conclusions................................................................................... 10
References........................................................................................ 11
G.Pavesi(*)
DepartmentofBiosciences,UniversityofMilan,ViaCeloria26,20133Milan,Italy
e-mail:[email protected]
2 G.Pavesi
1 Introduction: Chromatin Immunoprecipitation
and Next-Generation Sequencing
Theintroductionofnext-generationsequencing(NGS)technologieshasopenedup
newavenuesforeverytypeofgeneticandgenomicresearch[1,2].Oneofthefields
in which the impact of NGS has been more relevant is perhaps the study of gene
regulationatthetranscriptionallevel,andthesubsequentanalysisstepssuchasthe
constructionofregulatorynetworks.
Itisessentialforthedefinitionoftranscriptionregulatorynetworkstoestablish
correctrelationshipsbetweenregulatorssuchastranscriptionfactors(TFs)andthe
genestheyregulate[3],togetherwiththeeffectoftheactivityoftheTFs(activator
or repressor) [4]. A fundamental step forward in this direction has been made
possible by lab techniques enabling the large-scale identification of TF-DNA
binding sites on the genome, with experiments simply impossible to perform just
afewyearsago.
Chromatin is a complex of DNA and proteins that forms chromosomes within
the nucleus of eukaryotic cells. Chromatin Immunoprecipitation (ChIP) [5] is a
techniqueenablingtheextractionfromthecell nucleus ofaspecific protein-DNA
chromatin complex, including DNA binding proteins such as TFs. The different
stepsofaChIPexperimentaresummarizedinFig.1.Firstofall,theDNA-bound
proteinsare cross-linked, thatis, fixed tothe DNA. Thecross-linkedchromatinis
usuallyshearedbysonication,providingfragmentsof300–1,000basepairs(bps)in
length.Thenaspecificantibodythatrecognizesonlytheprotein(TF)ofinterestis
employed,and the antibody, boundtothe TF which inturn is boundtothe DNA,
permits the selective extraction and isolation of the chromatin complex. At this
point, DNA is released from the TF by reverse-crosslinking and purified, and the
resultisaDNAsampleenrichedinregionscorrespondingtothegenomiclocations
of the sites that were bound in vivo by the TF (or, in general, the DNA-binding
protein) studied. The experiment is performed on thousands of cells at the same
time so as to have a quantity of DNA suitable for further analysis and to have
enough “enrichment” in the sample, that is, enough copies of each of the DNA
regionsboundbytheTF,todiscriminatethemfromexperimentalnoise.
The next phase is quite logically the identification of the DNA regions them-
selves – and of their corresponding location in the genome. The introduction of
“tilingarrays”hadpermittedforthefirsttimetheanalysisoftheDNAextractedon
awhole-genomescale(ChIPonChip[4,6])byusingprobesdesignedtocoverthe
sequence of a whole genome, or a subset of genomic regions of interest (such as
withpromoterarrays).TheintroductionofNGStechnologieshasenabledthistype
ofexperimenttomoveonestepfurtherbyprovidingatreasonablecostperhapsthe
simplest solution: to identify the DNA extracted by the cell by immunoprecipita-
tion,sequencetheDNAitself(ChIPSequencing,orChIP-Seq[5,7]).
Without delving into technical details, given a double-stranded DNA fragment
derivedasjustdescribed,sequencingdeterminesthenucleotidesequenceoneither
strand,movingfromthe50 to30 direction,orbothstrandssimultaneously (paired-
