Table Of ContentJinhu Lü
Pei Wang
Modeling
and Analysis
of Bio-molecular
Networks
Modeling and Analysis of Bio-molecular Networks
¨
Jinhu Lu • Pei Wang
Modeling and Analysis
of Bio-molecular Networks
JinhuLu¨ PeiWang
SchoolofAutomationScience SchoolofMathematicsandStatistics
andElectricalEngineering HenanUniversity
StateKeyLaboratoryofSoftware Kaifeng
DevelopmentEnvironment Henan,China
BeijingAdvancedInnovationCenterforBig
DataandBrainComputing
BeihangUniversity
Beijing,China
ISBN978-981-15-9143-3 ISBN978-981-15-9144-0 (eBook)
https://doi.org/10.1007/978-981-15-9144-0
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Preface
Systems biology is an interdisciplinary scientific area, which aims at system-
level understanding of biological systems. It applies mathematical modeling, as
well as computational and statistical analysis techniques to explore complex
biological systems. Biological systems can be described by different levels of
bio-molecularnetworks, which include gene regulatory networks, protein–protein
interaction networks, metabolic networks, signal transduction networks, gene co-
expression networks, etc. Different networks contain different biological entities
andinteractiverelationships.Theinvestigationsonbio-molecularnetworkscanhelp
us to understand the origin, development, and evolution of life phenomena at the
systemslevel.Theycanalso provideinsightsaswellas real-worldapplicationsto
medicineandlifesciences.
This book aims to introduce the mathematical modeling, as well as dynamical
andstatistical analysison severaltypicalbio-molecularnetworks.We will discuss
thetopicsonthereconstructionofbio-molecularnetworks,mathematicalmodeling
methodsforgeneregulatorynetworks,dynamicalanalysisofseveralsimplegenetic
circuits(alsowellknownasnetworkmotifs)aswellasstatisticalanalysisonsome
large-scalebio-molecularnetworks. Finally, we also introducethe readersa focus
research field that is full of opportunities and challenges—data-driven statistical
approaches for omics data analysis. The detailed organization of the book is as
follows.
In Chap.1, we introduce the related backgrounds of this book, where we
review the basic concepts and discuss the brief history of systems biology and
thecomplexnetworksscience.Moreover,weintroducesometraditionalmetricsfor
complexnetworksand statistical analysismethodsforpracticalproblems.Finally,
weintroducesomesoftwaretoolstoperformdynamicalandstatisticalanalysis,as
wellastovisualizecomplexdata.
In Chap.2, we introduce some methods for reconstructing bio-molecular net-
works.Fourapproachesforbio-molecularnetworksreconstructionwerediscussed,
namely: (1) construction of bio-molecular networks based on online databases;
(2)generatingbio-molecularnetworksthroughartificialalgorithmsthatmimicthe
general features of real-world networks, such as those based on the duplication
vii
viii Preface
and divergence mechanisms; (3) inferring bio-molecular networks via various
mathematical and statistical models based on behavioral data of bio-molecules;
and (4) topologyidentification based on dynamicalsystem theory.We summarize
some online databases, various artificial algorithms, mathematical and statistical
methods to reconstruct each type of bio-molecular networks. The reconstruction
ofbio-molecularnetworksfacilitatesthefurthermathematicalmodeling,dynamical
andstatisticalanalysisonthem.
Chapter 3 deals with the mathematical modeling and dynamical analysis of
severalsimplegeneticcircuits.Thewholebio-molecularnetworksformodelorgan-
isms are too complex,which have hindered our understandingof them. However,
it was found that real-world bio-molecular networks consist of network motifs.
Networkmotifsarethosesimplecircuitsthatappearedfarfrequentlythanthatinits
randomizedcounterparts.Theinvestigationsonnetworkmotifsarethefirststepto
systems-levelexploration.Throughmathematicalmodelinganddynamicalanalysis,
weclassifythestructuraladvantagesofseveralsimplecircuits.InChaps.4and5,we
overviewanddiscussthemodelinganddynamicalanalysisofseveralcoupledand
large-sizedgeneregulatorynetworks,whichgraduallypromoteourexplorationsof
bio-molecularnetworkstosystemslevel.
Based on statistical analysis and the duplication-divergencemodel, we clarify
severalevolutionarymechanismsofnetworkmotifsinundirectedproteininteraction
networks in Chap.6. In Chaps.7 and 8, for large-scale bio-molecular networks,
we introduce some methods on the identification of importantnodes (also known
as gene prioritization)in biologicalnetworksand clarify the statistical featuresof
some functionalgenes in large-scale human protein–proteininteraction networks.
Chapter 9 deals with the topic of data-driven approachesfor omics data analysis,
and some classical methods in this area have been introduced. Especially, we
summarized some typical statistical models with different penalization terms (for
differentpurposesduringdataanalysis).
The topics discussed in this book cover four aspects: bio-molecular network
reconstruction; mathematical modeling and dynamical analysis of bio-molecular
networks;statisticalanalysisofbio-molecularnetworks;data-drivenmathematical
modeling and statistical analysis of biological systems. Some of the methods
introducedin this bookare adaptedfrom our publishedpapers.This bookhas the
followingmerits:
1. Introducesvariousapproachestoreconstructbio-molecularnetworks.
2. Covers the analysis of various networks ranging from simple circuits, middle-
sizednetworks,tolarge-scalebio-molecularnetworks.
3. Introduces various dynamical and statistical analysis tools for gene regulatory
networksandproteininteractionnetworks.
The expected audience of this book are undergraduates, graduates, and
researcherswhoareinterestedinsystemsbiology,dynamicalsystems,andcomplex
networks. Prerequisites needed to understand this book include complex network
theory, multivariate statistical analysis theory, linear algebra, matrix theory, and
theoriesofdynamicalsystems.
Preface ix
Due to the festinate time and limited knowledgeof the authors, some mistakes
and errors in the book are unavoidable. Thus, we welcome to all readers to bring
toourattentionanyerrorstheymayfindinthebookandalsogivesuggestionsfor
adding new material to improve this book. We hope that this book can help our
audienceduringtheirexplorationofthetruthofnature.
Beijing,China JinhuLü
Kaifeng,China PeiWang
May2020
Acknowledgments
We acknowledgemany people who have contributed in various ways to the com-
pletionofthisbook.Firstofall,Iwouldliketothankmanyacademicpredecessors
for their long-term academic guidance, support and help, including the following
academicians: Prof. Lei Guo (CAS), Prof. Bohu Li (BAUU), Prof. Weimin Bao
(BAUU),Prof.JinpengHuai(BAUU),Prof.JianchengFang(BAUU),Prof.Zhiming
Zheng (BAUU), Prof. Wei Li (BAUU), Prof. Jun Zhang (BIT), Prof. Jifeng He
(ECNU),Prof.JianhuaLu(TsinghuaU),Prof.HaoYing(CAMS),Prof.WeiWang
(CASC),Prof.JieJiang(CASC),Prof.ZhongbenXu(XJTU),Prof.XiaohongGuan
(XJTU),Prof.TieniuTan(CAS)andProf.GuangrenDuan(HIT).Sorry,Icanonly
mentionafewofthemduetothespacelimitation.
WealsowanttoexpressourappreciationtoProfessorJun-anLuattheSchoolof
MathematicsandStatistics,WuhanUniversity,ProfessorXinghuoYuattheSchool
ofElectricalandComputerEngineering,RMITUniversity,andProfessorTianshou
ZhouattheSunYat-senUniversityfordiscussionofsomecontentsinthisbook.We
thankShuangXu,MingqiuLi,PeipeiHuang,CanWei,QiongXu,LinglingWang,
Chunfang Liu, Shunjie Chen, and Lixin Li for their help during the preparation
of the book. Dr. Shuang Xu has contributed to some contents in Chaps.2 and 7.
Dr.HaiboGu,QiongXu,andLinglingWanghavecontributedtohelpustoapply
fortherightsandpermissionstoreusesomefiguresandcontentsofsomepublished
papers.Wearealsothankfulforthesupportandencouragementfromourcolleagues
andfamilies.
ThisworkwassupportedinpartbytheNationalKeyResearchandDevelopment
ProgramofChinaunderGrants2016YFB0800401,inpartbytheNationalNatural
ScienceFoundationofChinaunder61532020and61773153.Itwasalsosponsored
byNaturalScienceFoundationofHenanundergrant202300410045,theProgram
for Science and TechnologyInnovationTalents in Universities of Henan Province
under grant 20HASTIT025, and the Training Plan of Young Key Teachers in
CollegesandUniversitiesofHenanProvinceundergrant2018GGJS021.
xi
Contents
1 IntroductionandPreliminaries............................................. 1
1.1 SystemsBiology ........................................................ 1
1.1.1 Overviews....................................................... 1
1.1.2 Developments................................................... 3
1.1.3 ImplicationsandApplications ................................. 4
1.2 ComplexNetworks...................................................... 6
1.2.1 Overviews....................................................... 6
1.2.2 MathematicalDescription...................................... 7
1.2.3 FourTypesofNetworks........................................ 7
1.2.4 StatisticalMetricsofNetworks ................................ 14
1.2.5 DatasetsforReal-WorldComplexNetworks.................. 19
1.3 CentralDogmaofMolecularBiology ................................. 23
1.4 Bio-MolecularNetworks ............................................... 24
1.5 SeveralStatisticalMethods............................................. 25
1.5.1 DescriptiveStatistics ........................................... 25
1.5.2 ClusterAnalysis ................................................ 29
1.5.3 PrincipalComponentAnalysis................................. 33
1.6 SoftwareforNetworkVisualizationandAnalysis..................... 34
1.6.1 Pajek............................................................. 34
1.6.2 Gephi............................................................ 34
1.6.3 Cytoscape ....................................................... 35
1.6.4 MATLABPackagesandOthers................................ 35
1.7 SoftwareforStatisticalandDynamicalAnalysis...................... 38
1.7.1 SAS.............................................................. 38
1.7.2 SPSS............................................................. 38
1.7.3 MATLAB ....................................................... 39
1.7.4 R................................................................. 40
1.7.5 SomeOtherSoftware........................................... 41
1.8 OrganizationoftheBook............................................... 43
References..................................................................... 44
xiii
