Skip to main content
SpringerLink
Log in

Modular Organization and Emergence in Systems Biology

  • Chapter
  • First Online:
Book cover Emergence and Modularity in Life Sciences

Abstract

Understanding, how cellular functions emerge from the interaction of biological components, is the main goal of systems biology. Here, we review the relevance of a modular organization and the emergence of collective dynamical states in systems biology and show that the concept of networks (i.e., the representation of biological systems in terms of nodes and links) allows us to formally define modularity and to quantitatively assess the impact of modularity on the emergent dynamical behaviors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Arenas A, Diaz-Guilera A (2007) Synchronization and modularity in complex networks. Eur Phys J Spec Top 143(1):19–25

    Article  Google Scholar 

  • Arenas A, Diaz-Guilera A, Pérez-Vicente CJ (2006) Synchronization reveals topological scales in complex networks. Phys Rev Lett 96(11):114,102

    Article  CAS  Google Scholar 

  • Arenas A, Díaz-Guilera A, Kurths J, Moreno Y, Zhou C (2008) Synchronization in complex networks. Phys Rep 469(3):93–153

    Article  Google Scholar 

  • Auffray C, Chen Z, Hood L (2009) Systems medicine: the future of medical genomics and healthcare. Genome Med 1(1):2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Babu MM, Luscombe NM, Aravind L, Gerstein M, Teichmann SA (2004) Structure and evolution of transcriptional regulatory networks. Curr Opin Struct Biol 14(3):283–291

    Article  CAS  PubMed  Google Scholar 

  • Badimon L, Vilahur G, Padro T (2017) Systems biology approaches to understand the effects of nutrition and promote health. Br J Clin Pharmacol 83(1):38–45

    Article  PubMed  Google Scholar 

  • Barabási AL (2016) Network science. Cambridge University Press

    Google Scholar 

  • Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell’s functional organization. Nat Rev Genet 5(2):101

    Article  CAS  PubMed  Google Scholar 

  • Barabási AL, Gulbahce N, Loscalzo J (2011) Network medicine: a network-based approach to human disease. Nat. Rev Genet 12(1):56

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bauer CR, Knecht C, Fretter C, Baum B, Jendrossek S, Rühlemann M, Heinsen FA, Umbach N, Grimbacher B, Franke A et al (2017) Interdisciplinary approach towards a systems medicine toolbox using the example of inflammatory diseases. Brief Bioinf 18(3):479–487

    Google Scholar 

  • Beber ME, Fretter C, Jain S, Sonnenschein N, Müller-Hannemann M, Hütt MT (2012) Artefacts in statistical analyses of network motifs: general framework and application to metabolic networks. J R Soc. Interface p:rsif20120490

    Google Scholar 

  • Beber ME, Armbruster D, Hütt MT (2013) The prescribed output pattern regulates the modular structure of flow networks. Eur Phys J B 86(11):473

    Article  CAS  Google Scholar 

  • Bork P, Jensen LJ, Von Mering C, Ramani AK, Lee I, Marcotte EM (2004) Protein interaction networks from yeast to human. Curr Opin Struct Biol 14(3):292–299

    Article  CAS  PubMed  Google Scholar 

  • Clune J, Mouret JB, Lipson H (2013) The evolutionary origins of modularity. Proc R Soc B 280(1755):20122,863

    Article  Google Scholar 

  • Costanzo M, VanderSluis B, Koch EN, Baryshnikova A, Pons C, Tan G, Wang W, Usaj M, Hanchard J, Lee SD et al (2016) A global genetic interaction network maps a wiring diagram of cellular function. Science 353(6306):aaf1420

    Google Scholar 

  • Csete M, Doyle J (2004) Bow ties, metabolism and disease. TRENDS in Biotechnology 22(9):446–450

    Article  CAS  PubMed  Google Scholar 

  • Damicelli F, Hilgetag CC, Hütt MT, Messé A (2017) Modular topology emerges from plasticity in a minimalistic excitable network model. Chaos: An Interdisciplinary Journal of Nonlinear Science 27(4):047,406

    Article  Google Scholar 

  • De Domenico M, Lancichinetti A, Arenas A, Rosvall M (2015) Identifying modular flows on multilayer networks reveals highly overlapping organization in interconnected systems. Phys Rev X 5(1):011,027

    Google Scholar 

  • De Menezes MA, Barabási AL (2004) Fluctuations in network dynamics. Phys Rev Lett 92(2):028,701

    Google Scholar 

  • Enders M, Hütt MT, Jeschke JM (2018) Drawing a map of invasion biology based on a network of hypotheses. Ecosphere 9(3):e02,146

    Article  Google Scholar 

  • Erdős P, Rényi A (1959) On random graphs, i. Publ Math (Debrecen) 6:290–297

    Google Scholar 

  • Fortunato S (2010) Community detection in graphs. Phys Rep 486(3–5):75–174

    Article  Google Scholar 

  • Fortunato S, Hric D (2016) Community detection in networks: a user guide. Phys Rep 659:1–44

    Article  Google Scholar 

  • Fretter C, Müller-Hannemann M, Hütt MT (2012) Subgraph fluctuations in random graphs. Phys Rev E 85(5):056,119

    Article  CAS  Google Scholar 

  • Garcia GC, Lesne A, Hütt MT, Hilgetag CC (2012) Building blocks of self-sustained activity in a simple deterministic model of excitable neural networks. Front Comput Neurosci 6:50

    Article  PubMed  PubMed Central  Google Scholar 

  • Girvan M, Newman ME (2002) Community structure in social and biological networks. Proc Natl Acad Sci 99(12):7821–7826

    Article  CAS  Google Scholar 

  • Goh KI, Choi IG (2012) Exploring the human diseasome: the human disease network. Brief Funct Gen 11(6):533–542

    Article  CAS  Google Scholar 

  • Guimera R, Amaral LAN (2005) Functional cartography of complex metabolic networks. Nature 433(7028):895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guimera R, Sales-Pardo M, Amaral LAN (2004) Modularity from fluctuations in random graphs and complex networks. Phys Rev E 70(2):025,101

    Article  CAS  Google Scholar 

  • Han JDJ, Bertin N, Hao T, Goldberg DS, Berriz GF, Zhang LV, Dupuy D, Walhout AJ, Cusick ME, Roth FP et al (2004) Evidence for dynamically organized modularity in the yeast protein-protein interaction network. Nature 430(6995):88

    Article  CAS  PubMed  Google Scholar 

  • Hartwell LH, Hopfield JJ, Leibler S, Murray AW (1999) From molecular to modular cell biology. Nature 402(6761supp):C47

    Article  CAS  PubMed  Google Scholar 

  • Helikar T, Konvalina J, Heidel J, Rogers JA (2008) Emergent decision-making in biological signal transduction networks. Proc Nat Acad Sci 105(6):1913–1918

    Article  CAS  PubMed  Google Scholar 

  • Hopkins AL (2008) Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol 4(11):682

    Article  CAS  PubMed  Google Scholar 

  • Hütt MT (2014) Understanding genetic variation-the value of systems biology. Br J Clin Pharmacol 77(4):597–605

    Article  PubMed  PubMed Central  Google Scholar 

  • Hütt MT, Kaiser M, Hilgetag CC (2014) Perspective: network-guided pattern formation of neural dynamics. Phil Trans R Soc B 369(1653):20130,522

    Article  Google Scholar 

  • Jeong H, Mason SP, Barabási AL, Oltvai ZN (2001) Lethality and centrality in protein networks. Nature 411(6833):41

    Article  CAS  PubMed  Google Scholar 

  • Kashtan N, Alon U (2005) Spontaneous evolution of modularity and network motifs. Proc Nat Acad Sci U S A 102(39):13,773–13,778

    Article  CAS  Google Scholar 

  • Kitano H (2002a) Computational systems biology. Nature 420(6912):206

    Article  CAS  PubMed  Google Scholar 

  • Kitano H (2002b) Systems biology: a brief overview. Science 295(5560):1662–1664

    Article  CAS  PubMed  Google Scholar 

  • Kitano H (2004) Biological robustness. Nat Rev Genet 5(11):826

    Article  CAS  PubMed  Google Scholar 

  • Knecht C, Fretter C, Rosenstiel P, Krawczak M, Hütt MT (2016) Distinct metabolic network states manifest in the gene expression profiles of pediatric inflammatory bowel disease patients and controls. Sci Rep 6(32):584

    Google Scholar 

  • Kosmidis K, Beber M, Hütt MT (2015) Network heterogeneity and node capacity lead to heterogeneous scaling of fluctuations in random walks on graphs. Adv Complex Syst 18(01n02):1550,007

    Article  Google Scholar 

  • Kreimer A, Borenstein E, Gophna U, Ruppin E (2008) The evolution of modularity in bacterial metabolic networks. Proc Nat Acad Sci 105(19):6976–6981

    Article  CAS  PubMed  Google Scholar 

  • Kuramoto Y (1984) Chemical oscillations, waves and turbulence

    Google Scholar 

  • Li S, Assmann SM, Albert R (2006) Predicting essential components of signal transduction networks: a dynamic model of guard cell abscisic acid signaling. PLoS Biol 4(10):e312

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ma HW, Zeng AP (2003) The connectivity structure, giant strong component and centrality of metabolic networks. Bioinformatics 19(11):1423–1430

    Article  CAS  PubMed  Google Scholar 

  • Marr C, Theis FJ, Liebovitch LS, Hütt MT (2010) Patterns of subnet usage reveal distinct scales of regulation in the transcriptional regulatory network of escherichia coli. PLoS Comput Biol 6(7):e1000,836

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Maslov S, Sneppen K (2002) Specificity and stability in topology of protein networks. Science 296(5569):910–913

    Article  CAS  PubMed  Google Scholar 

  • Messé A, Hütt MT, König P, Hilgetag CC (2015) A closer look at the apparent correlation of structural and functional connectivity in excitable neural networks. Sci Rep 5:7870

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Messé A, Hütt MT, Hilgetag CC (2018) Toward a theory of coactivation patterns in excitable neural networks. PLoS Comput Biol14(4):e1006,084

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Meunier D, Lambiotte R, Bullmore ET (2010) Modular and hierarchically modular organization of brain networks. Front Neurosci 4:200

    Google Scholar 

  • Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U (2002) Network motifs: simple building blocks of complex networks. Science 298(5594):824–827

    Article  CAS  PubMed  Google Scholar 

  • Müller-Linow M, Hilgetag CC, Hütt MT (2008) Organization of excitable dynamics in hierarchical biological networks. PLoS Comput Biol 4(9):e1000,190

    Article  CAS  Google Scholar 

  • Newman ME (2004) Coauthorship networks and patterns of scientific collaboration. Proc Nat Acad Sci 101(suppl 1):5200–5205

    Article  CAS  Google Scholar 

  • Newman ME, Girvan M (2004) Finding and evaluating community structure in networks. Phys Rev E 69(2):026,113

    Article  CAS  Google Scholar 

  • Parter M, Kashtan N, Alon U (2007) Environmental variability and modularity of bacterial metabolic networks. BMC Evol Biol 7(1):169

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ravasz E, Somera AL, Mongru DA, Oltvai ZN, Barabási AL (2002) Hierarchical organization of modularity in metabolic networks. Science 297(5586):1551–1555

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues FA, Peron TKD, Ji P, Kurths J (2016) The kuramoto model in complex networks. Phys Rep 610:1–98

    Article  Google Scholar 

  • Rosvall M, Bergstrom C (2008) Maps of random walks on complex networks reveal community structure. Proc Nat Acad Sci 105:1118–1123

    Article  CAS  PubMed  Google Scholar 

  • Rosvall M, Esquivel AV, Lancichinetti A, West JD, Lambiotte R (2014) Memory in network flows and its effects on spreading dynamics and community detection. Nat Commun 5:4630

    Article  CAS  PubMed  Google Scholar 

  • Silverman EK, Loscalzo J (2013) Developing new drug treatments in the era of network medicine. Clin Pharmacol Ther 93(1):26–28

    Article  CAS  PubMed  Google Scholar 

  • Singh S, Samal A, Giri V, Krishna S, Raghuram N, Jain S (2013) Flux-based classification of reactions reveals a functional bow-tie organization of complex metabolic networks. Phys Rev E 87(5):052,708

    Google Scholar 

  • Sonnenschein N, Geertz M, Muskhelishvili G, Hütt MT (2011) Analog regulation of metabolic demand. BMC Syst Biol 5(1):40

    Article  PubMed  PubMed Central  Google Scholar 

  • Sonnenschein N, Dzib JFG, Lesne A, Eilebrecht S, Boulkroun S, Zennaro MC, Benecke A, Hütt MT (2012) A network perspective on metabolic inconsistency. BMC Syst Biol 6(1):41

    Article  PubMed  PubMed Central  Google Scholar 

  • Strogatz S (2001) Exploring complex networks. Nat 410(6825):268–76

    Article  CAS  Google Scholar 

  • Strogatz SH (2000) From kuramoto to crawford: exploring the onset of synchronization in populations of coupled oscillators. Phys D: Nonlinear Phenom 143(1):1–20

    Article  Google Scholar 

  • Voordijk H, Meijboom B, de Haan J (2006) Modularity in supply chains: a multiple case study in the construction industry. Int J Oper Prod Manag 26(6):600–618

    Article  Google Scholar 

  • Wagner GP, Pavlicev M, Cheverud JM (2007) The road to modularity. Nat Rev Genet 8(12):921

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Life Sciences and Chemistry, Jacobs University Bremen, 28759, Bremen, Germany

    Marc-Thorsten Hütt

Authors
  1. Marc-Thorsten Hütt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marc-Thorsten Hütt .

Editor information

Editors and Affiliations

  1. Karlsruher Institut für Technologie, Eggenstein-Leopoldshafen, Germany

    Lars H. Wegner

  2. FB Biologie, TU Darmstadt, Darmstadt, Germany

    Ulrich Lüttge

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hütt, MT. (2019). Modular Organization and Emergence in Systems Biology. In: Wegner, L., Lüttge, U. (eds) Emergence and Modularity in Life Sciences. Springer, Cham. https://doi.org/10.1007/978-3-030-06128-9_2

Download citation

Publish with us

Policies and ethics

Search

Navigation