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Modular Organization and Emergence in Systems Biology

  • Marc-Thorsten HüttEmail author
Chapter

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.

References

  1. Arenas A, Diaz-Guilera A (2007) Synchronization and modularity in complex networks. Eur Phys J Spec Top 143(1):19–25Google Scholar
  2. Arenas A, Diaz-Guilera A, Pérez-Vicente CJ (2006) Synchronization reveals topological scales in complex networks. Phys Rev Lett 96(11):114,102Google Scholar
  3. Arenas A, Díaz-Guilera A, Kurths J, Moreno Y, Zhou C (2008) Synchronization in complex networks. Phys Rep 469(3):93–153Google Scholar
  4. Auffray C, Chen Z, Hood L (2009) Systems medicine: the future of medical genomics and healthcare. Genome Med 1(1):2PubMedPubMedCentralGoogle Scholar
  5. Babu MM, Luscombe NM, Aravind L, Gerstein M, Teichmann SA (2004) Structure and evolution of transcriptional regulatory networks. Curr Opin Struct Biol 14(3):283–291PubMedGoogle Scholar
  6. 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):38–45PubMedGoogle Scholar
  7. Barabási AL (2016) Network science. Cambridge University PressGoogle Scholar
  8. Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell’s functional organization. Nat Rev Genet 5(2):101PubMedGoogle Scholar
  9. Barabási AL, Gulbahce N, Loscalzo J (2011) Network medicine: a network-based approach to human disease. Nat. Rev Genet 12(1):56PubMedPubMedCentralGoogle Scholar
  10. 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):479–487Google Scholar
  11. 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:rsif20120490Google Scholar
  12. Beber ME, Armbruster D, Hütt MT (2013) The prescribed output pattern regulates the modular structure of flow networks. Eur Phys J B 86(11):473Google Scholar
  13. 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):292–299PubMedGoogle Scholar
  14. Clune J, Mouret JB, Lipson H (2013) The evolutionary origins of modularity. Proc R Soc B 280(1755):20122,863Google Scholar
  15. 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):aaf1420Google Scholar
  16. Csete M, Doyle J (2004) Bow ties, metabolism and disease. TRENDS in Biotechnology 22(9):446–450PubMedGoogle Scholar
  17. 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):047,406Google Scholar
  18. 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):011,027Google Scholar
  19. De Menezes MA, Barabási AL (2004) Fluctuations in network dynamics. Phys Rev Lett 92(2):028,701Google Scholar
  20. Enders M, Hütt MT, Jeschke JM (2018) Drawing a map of invasion biology based on a network of hypotheses. Ecosphere 9(3):e02,146Google Scholar
  21. Erdős P, Rényi A (1959) On random graphs, i. Publ Math (Debrecen) 6:290–297Google Scholar
  22. Fortunato S (2010) Community detection in graphs. Phys Rep 486(3–5):75–174Google Scholar
  23. Fortunato S, Hric D (2016) Community detection in networks: a user guide. Phys Rep 659:1–44Google Scholar
  24. Fretter C, Müller-Hannemann M, Hütt MT (2012) Subgraph fluctuations in random graphs. Phys Rev E 85(5):056,119Google Scholar
  25. 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 6:50PubMedPubMedCentralGoogle Scholar
  26. Girvan M, Newman ME (2002) Community structure in social and biological networks. Proc Natl Acad Sci 99(12):7821–7826Google Scholar
  27. Goh KI, Choi IG (2012) Exploring the human diseasome: the human disease network. Brief Funct Gen 11(6):533–542Google Scholar
  28. Guimera R, Amaral LAN (2005) Functional cartography of complex metabolic networks. Nature 433(7028):895PubMedPubMedCentralGoogle Scholar
  29. Guimera R, Sales-Pardo M, Amaral LAN (2004) Modularity from fluctuations in random graphs and complex networks. Phys Rev E 70(2):025,101Google Scholar
  30. 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):88PubMedGoogle Scholar
  31. Hartwell LH, Hopfield JJ, Leibler S, Murray AW (1999) From molecular to modular cell biology. Nature 402(6761supp):C47PubMedGoogle Scholar
  32. Helikar T, Konvalina J, Heidel J, Rogers JA (2008) Emergent decision-making in biological signal transduction networks. Proc Nat Acad Sci 105(6):1913–1918PubMedGoogle Scholar
  33. Hopkins AL (2008) Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol 4(11):682PubMedGoogle Scholar
  34. Hütt MT (2014) Understanding genetic variation-the value of systems biology. Br J Clin Pharmacol 77(4):597–605PubMedPubMedCentralGoogle Scholar
  35. Hütt MT, Kaiser M, Hilgetag CC (2014) Perspective: network-guided pattern formation of neural dynamics. Phil Trans R Soc B 369(1653):20130,522Google Scholar
  36. Jeong H, Mason SP, Barabási AL, Oltvai ZN (2001) Lethality and centrality in protein networks. Nature 411(6833):41PubMedGoogle Scholar
  37. Kashtan N, Alon U (2005) Spontaneous evolution of modularity and network motifs. Proc Nat Acad Sci U S A 102(39):13,773–13,778Google Scholar
  38. Kitano H (2002a) Computational systems biology. Nature 420(6912):206PubMedGoogle Scholar
  39. Kitano H (2002b) Systems biology: a brief overview. Science 295(5560):1662–1664PubMedGoogle Scholar
  40. Kitano H (2004) Biological robustness. Nat Rev Genet 5(11):826PubMedGoogle Scholar
  41. 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):584Google Scholar
  42. 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):1550,007Google Scholar
  43. Kreimer A, Borenstein E, Gophna U, Ruppin E (2008) The evolution of modularity in bacterial metabolic networks. Proc Nat Acad Sci 105(19):6976–6981PubMedGoogle Scholar
  44. Kuramoto Y (1984) Chemical oscillations, waves and turbulenceGoogle Scholar
  45. 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):e312PubMedPubMedCentralGoogle Scholar
  46. Ma HW, Zeng AP (2003) The connectivity structure, giant strong component and centrality of metabolic networks. Bioinformatics 19(11):1423–1430PubMedGoogle Scholar
  47. 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):e1000,836PubMedPubMedCentralGoogle Scholar
  48. Maslov S, Sneppen K (2002) Specificity and stability in topology of protein networks. Science 296(5569):910–913PubMedGoogle Scholar
  49. 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 5:7870PubMedPubMedCentralGoogle Scholar
  50. Messé A, Hütt MT, Hilgetag CC (2018) Toward a theory of coactivation patterns in excitable neural networks. PLoS Comput Biol14(4):e1006,084PubMedPubMedCentralGoogle Scholar
  51. Meunier D, Lambiotte R, Bullmore ET (2010) Modular and hierarchically modular organization of brain networks. Front Neurosci 4:200Google Scholar
  52. 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):824–827PubMedGoogle Scholar
  53. Müller-Linow M, Hilgetag CC, Hütt MT (2008) Organization of excitable dynamics in hierarchical biological networks. PLoS Comput Biol 4(9):e1000,190Google Scholar
  54. Newman ME (2004) Coauthorship networks and patterns of scientific collaboration. Proc Nat Acad Sci 101(suppl 1):5200–5205Google Scholar
  55. Newman ME, Girvan M (2004) Finding and evaluating community structure in networks. Phys Rev E 69(2):026,113Google Scholar
  56. Parter M, Kashtan N, Alon U (2007) Environmental variability and modularity of bacterial metabolic networks. BMC Evol Biol 7(1):169PubMedPubMedCentralGoogle Scholar
  57. Ravasz E, Somera AL, Mongru DA, Oltvai ZN, Barabási AL (2002) Hierarchical organization of modularity in metabolic networks. Science 297(5586):1551–1555PubMedGoogle Scholar
  58. Rodrigues FA, Peron TKD, Ji P, Kurths J (2016) The kuramoto model in complex networks. Phys Rep 610:1–98Google Scholar
  59. Rosvall M, Bergstrom C (2008) Maps of random walks on complex networks reveal community structure. Proc Nat Acad Sci 105:1118–1123PubMedGoogle Scholar
  60. 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 5:4630PubMedGoogle Scholar
  61. Silverman EK, Loscalzo J (2013) Developing new drug treatments in the era of network medicine. Clin Pharmacol Ther 93(1):26–28PubMedGoogle Scholar
  62. 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):052,708Google Scholar
  63. Sonnenschein N, Geertz M, Muskhelishvili G, Hütt MT (2011) Analog regulation of metabolic demand. BMC Syst Biol 5(1):40PubMedPubMedCentralGoogle Scholar
  64. 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):41PubMedPubMedCentralGoogle Scholar
  65. Strogatz S (2001) Exploring complex networks. Nat 410(6825):268–76Google Scholar
  66. Strogatz SH (2000) From kuramoto to crawford: exploring the onset of synchronization in populations of coupled oscillators. Phys D: Nonlinear Phenom 143(1):1–20Google Scholar
  67. 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):600–618Google Scholar
  68. Wagner GP, Pavlicev M, Cheverud JM (2007) The road to modularity. Nat Rev Genet 8(12):921PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Life Sciences and ChemistryJacobs University BremenBremenGermany

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