The powerful law of the power law and other myths in network biology.

For almost 10 years, topological analysis of different large-scale biological networks (metabolic reactions, protein interactions, transcriptional regulation) has been highlighting some recurrent properties: power law distribution of degree, scale-freeness, small world, which have been proposed to confer functional advantages such as robustness to environmental changes and tolerance to random mutations. Stochastic generative models inspired different scenarios to explain the growth of interaction networks during evolution. The power law and the associated properties appeared so ubiquitous in complex networks that they were qualified as "universal laws". However, these properties are no longer observed when the data are subjected to statistical tests: in most cases, the data do not fit the expected theoretical models, and the cases of good fitting merely result from sampling artefacts or improper data representation. The field of network biology seems to be founded on a series of myths, i.e. widely believed but false ideas. The weaknesses of these foundations should however not be considered as a failure for the entire domain. Network analysis provides a powerful frame for understanding the function and evolution of biological processes, provided it is brought to an appropriate level of description, by focussing on smaller functional modules and establishing the link between their topological properties and their dynamical behaviour.

[1]  E. Levanon,et al.  Preferential attachment in the protein network evolution. , 2003, Physical review letters.

[2]  Raya Khanin,et al.  How Scale-Free Are Biological Networks , 2006, J. Comput. Biol..

[3]  S A Kauffman,et al.  Control circuits for determination and transdetermination. , 1973, Science.

[4]  S. Shen-Orr,et al.  Superfamilies of Evolved and Designed Networks , 2004, Science.

[5]  John Bohannon Investigating networks: the dark side. , 2009, Science.

[6]  Sarah A Teichmann,et al.  Novel specificities emerge by stepwise duplication of functional modules. , 2005, Genome research.

[7]  R. Thomas,et al.  Boolean formalization of genetic control circuits. , 1973, Journal of theoretical biology.

[8]  R. Solé,et al.  Evolving protein interaction networks through gene duplication. , 2003, Journal of theoretical biology.

[9]  E. Ostrom A General Framework for Analyzing Sustainability of Social-Ecological Systems , 2009, Science.

[10]  E. Raineri,et al.  Evolvability and hierarchy in rewired bacterial gene networks , 2008, Nature.

[11]  A. Wagner,et al.  2 Structural Properties of Metabolic Networks: Implications for Evolution and Modelling of Metabolism , 2022 .

[12]  I. Ispolatov,et al.  Duplication-divergence model of protein interaction network. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[13]  Hildegard Meyer-Ortmanns,et al.  Self-similar scale-free networks and disassortativity. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[14]  S. Shen-Orr,et al.  Network motifs in the transcriptional regulation network of Escherichia coli , 2002, Nature Genetics.

[15]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[16]  Sean R. Collins,et al.  Global landscape of protein complexes in the yeast Saccharomyces cerevisiae , 2006, Nature.

[17]  Albert-László Barabási,et al.  Error and attack tolerance of complex networks , 2000, Nature.

[18]  K. Gurney,et al.  Network ‘Small-World-Ness’: A Quantitative Method for Determining Canonical Network Equivalence , 2008, PloS one.

[19]  H E Stanley,et al.  Classes of small-world networks. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Jordi Bascompte,et al.  Disentangling the Web of Life , 2009, Science.

[21]  Walter Willinger,et al.  Towards a Theory of Scale-Free Graphs: Definition, Properties, and Implications , 2005, Internet Math..

[22]  R. Thomas,et al.  Logical analysis of systems comprising feedback loops. , 1978, Journal of theoretical biology.

[23]  Duncan J. Watts,et al.  Collective dynamics of ‘small-world’ networks , 1998, Nature.

[24]  Albert,et al.  Emergence of scaling in random networks , 1999, Science.

[25]  P. Bork,et al.  Proteome survey reveals modularity of the yeast cell machinery , 2006, Nature.

[26]  M. Elowitz,et al.  A synthetic oscillatory network of transcriptional regulators , 2000, Nature.

[27]  Denis Thieffry,et al.  Dynamical roles of biological regulatory circuits , 2007, Briefings Bioinform..

[28]  Nikos Kyrpides,et al.  Universal Protein Families and the Functional Content of the Last Universal Common Ancestor , 1999, Journal of Molecular Evolution.

[29]  R. Rosenfeld Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[30]  D. Fell,et al.  The small world of metabolism , 2000, Nature Biotechnology.

[31]  S. Shen-Orr,et al.  Network motifs: simple building blocks of complex networks. , 2002, Science.

[32]  John Bohannon,et al.  Counterterrorism's new tool: 'metanetwork' analysis. , 2009, Science.

[33]  Kirill Evlampiev,et al.  Conservation and topology of protein interaction networks under duplication-divergence evolution , 2008, Proceedings of the National Academy of Sciences.

[34]  Franck Picard,et al.  A mixture model for random graphs , 2008, Stat. Comput..

[35]  Uri Alon,et al.  Response to Comment on "Network Motifs: Simple Building Blocks of Complex Networks" and "Superfamilies of Evolved and Designed Networks" , 2004, Science.

[36]  M. Gerstein,et al.  Structure and evolution of transcriptional regulatory networks. , 2004, Current opinion in structural biology.

[37]  Michael Y. Galperin,et al.  Comparative genomics of the Archaea (Euryarchaeota): evolution of conserved protein families, the stable core, and the variable shell. , 1999, Genome research.

[38]  S. Atsumi,et al.  A synthetic phage λ regulatory circuit , 2006, Proceedings of the National Academy of Sciences.

[39]  Masanori Arita In silico atomic tracing by substrate-product relationships in Escherichia coli intermediary metabolism. , 2003, Genome research.

[40]  S. Wodak,et al.  Inferring meaningful pathways in weighted metabolic networks. , 2006, Journal of molecular biology.

[41]  J. Monod,et al.  Genetic regulatory mechanisms in the synthesis of proteins. , 1961, Journal of molecular biology.

[42]  M. E. J. Newman,et al.  Power laws, Pareto distributions and Zipf's law , 2005 .

[43]  A. Barabasi,et al.  Hierarchical Organization of Modularity in Metabolic Networks , 2002, Science.

[44]  Kirill Evlampiev,et al.  Modeling protein network evolution under genome duplication and domain shuffling , 2007, BMC Systems Biology.

[45]  A. Wagner The yeast protein interaction network evolves rapidly and contains few redundant duplicate genes. , 2001, Molecular biology and evolution.

[46]  Masanori Arita,et al.  Scale-freeness and biological networks. , 2005, Journal of biochemistry.

[47]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[48]  A. Vespignani Predicting the Behavior of Techno-Social Systems , 2009, Science.

[49]  J. van Helden,et al.  Metabolic pathfinding using RPAIR annotation. , 2009, Journal of molecular biology.

[50]  C. T. Butts,et al.  Revisiting the Foundations of Network Analysis , 2009, Science.

[51]  K. Tamura,et al.  Metabolic engineering of plant alkaloid biosynthesis. Proc Natl Acad Sci U S A , 2001 .

[52]  Evelyn Fox Keller,et al.  Revisiting "scale-free" networks. , 2005, BioEssays : news and reviews in molecular, cellular and developmental biology.

[53]  Masanori Arita The metabolic world of Escherichia coli is not small. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[54]  S. Lovell,et al.  Protein-protein interaction networks and biology—what's the connection? , 2008, Nature Biotechnology.

[55]  Albert-László Barabási,et al.  Scale-Free Networks: A Decade and Beyond , 2009, Science.

[56]  Wan Kyu Kim,et al.  Age-Dependent Evolution of the Yeast Protein Interaction Network Suggests a Limited Role of Gene Duplication and Divergence , 2008, PLoS Comput. Biol..

[57]  Albert-László Barabási,et al.  Hierarchical organization in complex networks. , 2003, Physical review. E, Statistical, nonlinear, and soft matter physics.

[58]  L. Glass,et al.  The logical analysis of continuous, non-linear biochemical control networks. , 1973, Journal of theoretical biology.

[59]  Carsten Wiuf,et al.  Subnets of scale-free networks are not scale-free: sampling properties of networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[60]  R. Albert,et al.  The large-scale organization of metabolic networks , 2000, Nature.

[61]  Thierry Emonet,et al.  Understanding Modularity in Molecular Networks Requires Dynamics , 2009, Science Signaling.

[62]  A. Barabasi,et al.  Lethality and centrality in protein networks , 2001, Nature.

[63]  David J. Galas,et al.  A duplication growth model of gene expression networks , 2002, Bioinform..

[64]  M. Kanehisa,et al.  Computational assignment of the EC numbers for genomic-scale analysis of enzymatic reactions. , 2004, Journal of the American Chemical Society.

[65]  김삼묘,et al.  “Bioinformatics” 특집을 내면서 , 2000 .

[66]  Lan V. Zhang,et al.  Evidence for dynamically organized modularity in the yeast protein–protein interaction network , 2004, Nature.

[67]  M. Gerstein,et al.  Genomic analysis of regulatory network dynamics reveals large topological changes , 2004, Nature.

[68]  Sarel J Fleishman,et al.  Comment on "Network Motifs: Simple Building Blocks of Complex Networks" and "Superfamilies of Evolved and Designed Networks" , 2004, Science.

[69]  Yves Deville,et al.  NeAT: a toolbox for the analysis of biological networks, clusters, classes and pathways , 2008, Nucleic Acids Res..

[70]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[71]  Philip M. Kim,et al.  Relating Three-Dimensional Structures to Protein Networks Provides Evolutionary Insights , 2006, Science.