Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system

Recently, the network paradigm, an application of graph theory to biology, has proven to be a powerful approach to gaining insights into biological complexity, and has catalyzed the advancement of systems biology. In this perspective and focusing on the immune system, we propose here a more comprehensive view to go beyond the concept of network. We start from the concept of degeneracy, one of the most prominent characteristic of biological complexity, defined as the ability of structurally different elements to perform the same function, and we show that degeneracy is highly intertwined with another recently-proposed organizational principle, i.e. 'bow tie architecture'. The simultaneous consideration of concepts such as degeneracy, bow tie architecture and network results in a powerful new interpretative tool that takes into account the constructive role of noise (stochastic fluctuations) and is able to grasp the major characteristics of biological complexity, i.e. the capacity to turn an apparently chaotic and highly dynamic set of signals into functional information.

[1]  Melvin Cohn,et al.  Degeneracy, mimicry and crossreactivity in immune recognition. , 2005, Molecular immunology.

[2]  Joachim L Schultze,et al.  Degeneracy instead of specificity: is this a solution to cancer immunotherapy? , 2002, Trends in immunology.

[3]  O. Berg,et al.  Kinetics of synonymous codon change for an amino acid of arbitrary degeneracy , 2004, Journal of Molecular Evolution.

[4]  G. Gamow Possible Relation between Deoxyribonucleic Acid and Protein Structures , 1954, Nature.

[5]  G. Edelman,et al.  Degeneracy and complexity in biological systems , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Gordon B Mills,et al.  Network topology determines dynamics of the mammalian MAPK1,2 signaling network: bifan motif regulation of C‐Raf and B‐Raf isoforms by FGFR and MC1R , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  Claudio Franceschi,et al.  Ecoimmunology: is there any room for the neuroendocrine system? , 2008, BioEssays : news and reviews in molecular, cellular and developmental biology.

[8]  Attila Priplata,et al.  Noise-enhanced human balance control. , 2002, Physical review letters.

[9]  Francis Crick,et al.  On Degenerate Templates and the Adaptor Hypothesis: A Note for the RNA Tie Club , 1955 .

[10]  B. Dahlmann Role of proteasomes in disease , 2007, BMC Biochemistry.

[11]  Sudarshan P. Purushothaman,et al.  Functions of bifans in context of multiple regulatory motifs in signaling networks. , 2007, Biophysical journal.

[12]  P. Dirac Quantum Mechanics of Many-Electron Systems , 1929 .

[13]  Alexey Zaikin,et al.  Towards quantitative prediction of proteasomal digestion patterns of proteins , 2008, 0806.2594.

[14]  H. Kitano,et al.  Robustness trade-offs and host–microbial symbiosis in the immune system , 2006, Molecular systems biology.

[15]  Jerne Nk Towards a network theory of the immune system. , 1974 .

[16]  H. Eisen,et al.  Degeneracy in the secondary immune response: stimulation of antibody formation by cross-reacting antigens. , 1969, Israel journal of medical sciences.

[17]  Karl J. Friston,et al.  Degeneracy and cognitive anatomy , 2002, Trends in Cognitive Sciences.

[18]  Ohad Parnes,et al.  From interception to incorporation: degeneracy and promiscuous recognition as precursors of a paradigm shift in immunology. , 2004, Molecular immunology.

[19]  A. Barabasi,et al.  The human disease network , 2007, Proceedings of the National Academy of Sciences.

[20]  Juliane Liepe,et al.  The 20S Proteasome Splicing Activity Discovered by SpliceMet , 2010, PLoS Comput. Biol..

[21]  Gastone Castellani,et al.  Stable State Analysis of an Immune Network Model , 1998 .

[22]  M. Delbrück The interaction of inert gases , 1930 .

[23]  Marius Usher,et al.  Stochastic resonance in the speed of memory retrieval , 2000, Biological Cybernetics.

[24]  Tilman Grune,et al.  Immunoproteasome and LMP2 polymorphism in aged and Alzheimer's disease brains , 2006, Neurobiology of Aging.

[25]  Peter R Jungblut,et al.  Intermediate-type 20 S proteasomes in HeLa cells: "asymmetric" subunit composition, diversity and adaptation. , 2007, Journal of molecular biology.

[26]  A. Perelson,et al.  Polyspecificity of T cell and B cell receptor recognition. , 2007, Seminars in immunology.

[27]  Francis Crick,et al.  The Present Position of the Coding Problem , 1959 .

[28]  Jing Zhao,et al.  Hierarchical modularity of nested bow-ties in metabolic networks , 2006, BMC Bioinformatics.

[29]  F. Ayala,et al.  Studies in the Philosophy of Biology , 1974 .

[30]  Crick Fh,et al.  Biochemical activities of nucleic acids. The present position of the coding problem. , 1959 .

[31]  H. Eisen,et al.  Specificity and degeneracy in antigen recognition: yin and yang in the immune system. , 2001, Annual review of immunology.

[32]  P. Reimann Brownian motors: noisy transport far from equilibrium , 2000, cond-mat/0010237.

[33]  N. Gay,et al.  Structure and function of Toll receptors and their ligands. , 2007, Annual review of biochemistry.

[34]  M. Larché,et al.  Allergen isoforms for immunotherapy: diversity, degeneracy and promiscuity , 1999, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[35]  A. Tartar,et al.  Confronting the degeneracy of convergent combinatorial immunogens, or 'mixotopes', with the specificity of recognition of the target sequences. , 1997, Vaccine.

[36]  B. Beutler TLRs and innate immunity. , 2009, Blood.

[37]  F H CRICK Biochemical activities of nucleic acids. The present position of the coding problem. , 1959, Brookhaven symposia in biology.

[38]  Gürol M. Süel,et al.  Biological role of noise encoded in a genetic network motif , 2010, Proceedings of the National Academy of Sciences.

[39]  G. E. W. Wolstenholme,et al.  Ciba Foundation Symposium - Control Processes in Multicellular Organisms , 1970 .

[40]  Axel Bender,et al.  Degeneracy: a design principle for achieving robustness and evolvability. , 2009, Journal of theoretical biology.

[41]  G N Lewis,et al.  THE THERMODYNAMICS OF GASES WHICH SHOW DEGENERACY (ENTARTUNG). , 1929, Proceedings of the National Academy of Sciences of the United States of America.

[42]  G. Edelman Group selection and phasic reentrant signaling a theory of higher brain function , 1982 .

[43]  H P Yockey Can the central dogma by derived from information theory? , 1978, Journal of theoretical biology.

[44]  E. Sercarz,et al.  Degenerate recognition of a dissimilar antigenic peptide by myelin basic protein-reactive T cells. Implications for thymic education and autoimmunity. , 1993, Journal of immunology.

[45]  Karan P. Singh,et al.  Theoretical Biology and Medical Modelling , 2007 .

[46]  J. Doyle,et al.  Bow Ties, Metabolism and Disease , 2022 .

[47]  Oreste Acuto,et al.  Tailoring T-cell receptor signals by proximal negative feedback mechanisms , 2008, Nature Reviews Immunology.

[48]  G. Beer,et al.  Order and Life , 1936, Nature.

[49]  D. Mason,et al.  A very high level of crossreactivity is an essential feature of the T-cell receptor. , 1998, Immunology today.

[50]  K. H. Grobman,et al.  Degeneracy and redundancy in cognitive anatomy , 2003 .

[51]  Gerald M. Edelman,et al.  Through a Computer Darkly: Group Selection and Higher Brain Function , 1982 .

[52]  G. Edelman Biochemistry and the Sciences of Recognition , 2004, Journal of Biological Chemistry.

[53]  Y Asano,et al.  Age-related degeneracy of T cell repertoire: influence of the aged environment on T cell allorecognition. , 1990, Gerontology.

[54]  Melvin Cohn,et al.  An in depth analysis of the concept of “polyspecificity” assumed to characterize TCR/BCR recognition , 2008, Immunologic research.

[55]  Massimo Marchiori,et al.  Quantifying the relevance of different mediators in the human immune cell network , 2004, Bioinform..

[56]  Natalia Polouliakh,et al.  Comparative Genomic Analysis of Transcription Regulation Elements Involved in Human Map Kinase G-protein Coupling Pathway , 2006, J. Bioinform. Comput. Biol..

[57]  Gregoire Nicolis,et al.  Stochastic resonance , 2007, Scholarpedia.

[58]  Cathy J Price,et al.  Convergence, degeneracy and control. , 2006, Language learning.

[59]  D. Fell,et al.  The small world inside large metabolic networks , 2000, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[60]  N K Jerne,et al.  Towards a network theory of the immune system. , 1973, Annales d'immunologie.

[61]  G Tononi,et al.  Measures of degeneracy and redundancy in biological networks. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[62]  M. DePamphilis,et al.  HUMAN DISEASE , 1957, The Ulster Medical Journal.

[63]  M. Groll,et al.  Diversity of proteasomal missions: fine tuning of the immune response , 2007, Biological chemistry.

[64]  G. Weisbuch,et al.  Immunology for physicists , 1997 .

[65]  Dominik Wodarz,et al.  Ecological and evolutionary principles in immunology. , 2006, Ecology letters.

[66]  Jonathan Timmis,et al.  Theoretical advances in artificial immune systems , 2008, Theor. Comput. Sci..

[67]  A. Abbas,et al.  Comprar Cellular and Molecular Immunology, Updated Edition, 6th Edition With STUDENT CONSULT Online Access | Abul K. Abbas | 9781416031239 | Saunders , 2009 .

[68]  G. Edelman,et al.  The Mindful Brain: Cortical Organization and the Group-Selective Theory of Higher Brain Function , 1978 .

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

[70]  Uri Alon,et al.  The immune-body cytokine network defines a social architecture of cell interactions , 2006, Biology Direct.

[71]  R T Damian,et al.  Parasite immune evasion and exploitation: reflections and projections , 1997, Parasitology.

[72]  Albert-László Barabási,et al.  Distribution of node characteristics in complex networks , 2007, Proceedings of the National Academy of Sciences.

[73]  Claudio Franceschi,et al.  Immunoproteasomes and immunosenescence , 2003, Ageing Research Reviews.

[74]  H. Kitano,et al.  G-Protein Coupled Receptor Signaling Architecture of Mammalian Immune Cells , 2009, PloS one.

[75]  Huba J. M. Kiss,et al.  Ageing as a price of cooperation and complexity , 2008, BioEssays : news and reviews in molecular, cellular and developmental biology.

[76]  G. Budd,et al.  On the origin and evolution of major morphological characters. , 2007, Biological reviews of the Cambridge Philosophical Society.

[77]  S Bornholdt,et al.  Robustness as an evolutionary principle , 2000, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[78]  G M Edelman,et al.  Selective Networks and Recognition Automata * , 1984, Annals of the New York Academy of Sciences.

[79]  J. Kurths,et al.  Coherence Resonance in a Noise-Driven Excitable System , 1997 .

[80]  G W Siskind,et al.  Degeneracy of antibody specificity. , 1983, Journal of immunology.

[81]  Clemencia Pinilla,et al.  Specificity and degeneracy of T cells. , 2004, Molecular immunology.

[82]  G. Edelman The Problem of Molecular Recognition by a Selective System , 1974 .

[83]  Joseph K. Pickrell,et al.  Evolutionary Dynamics of Human Toll-Like Receptors and Their Different Contributions to Host Defense , 2009, PLoS genetics.

[84]  Petter Holme,et al.  Subnetwork hierarchies of biochemical pathways , 2002, Bioinform..

[85]  G Tononi,et al.  A complexity measure for selective matching of signals by the brain. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[86]  H. Kitano Systems Biology: A Brief Overview , 2002, Science.

[87]  T. Poeschel,et al.  Peptide-size–dependent active transport in the proteasome , 2003 .

[88]  An-Ping Zeng,et al.  The Connectivity Structure, Giant Strong Component and Centrality of Metabolic Networks , 2003, Bioinform..

[89]  Bernard Malissen,et al.  What guides MHC-restricted TCR recognition? , 2007, Seminars in immunology.

[90]  H. Kitano,et al.  A comprehensive map of the toll-like receptor signaling network , 2006, Molecular systems biology.

[91]  Isidro Ferrer,et al.  Neuronal Induction of the Immunoproteasome in Huntington's Disease , 2003, The Journal of Neuroscience.

[92]  Andrei Z. Broder,et al.  Graph structure in the Web , 2000, Comput. Networks.

[93]  A. Abbas,et al.  Cellular and Molecular Immunology , 1991 .

[94]  J. Derisi,et al.  Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise , 2006, Nature.

[95]  F. Crick,et al.  The genetic code--yesterday, today, and tomorrow. , 1966, Cold Spring Harbor symposia on quantitative biology.

[96]  Michelle Lampl,et al.  Cellular life histories and bow tie biology , 2005, American journal of human biology : the official journal of the Human Biology Council.

[97]  U. Alon Network motifs: theory and experimental approaches , 2007, Nature Reviews Genetics.

[98]  Shoichi Kai,et al.  Noise-induced entrainment and stochastic resonance in human brain waves. , 2002, Physical review letters.

[99]  Silke Meiners,et al.  Multiple cardiac proteasome subtypes differ in their susceptibility to proteasome inhibitors. , 2010, Cardiovascular research.

[100]  H. Kröger,et al.  [Protein synthesis]. , 1974, Fortschritte der Medizin.

[101]  Sandra D'Alfonso,et al.  Immunoproteasome LMP2 60HH Variant Alters MBP Epitope Generation and Reduces the Risk to Develop Multiple Sclerosis in Italian Female Population , 2010, PloS one.

[102]  Ofer Feinerman,et al.  Quantitative challenges in understanding ligand discrimination by alphabeta T cells. , 2008, Molecular immunology.

[103]  A. Iwasaki,et al.  Toll-like receptor control of the adaptive immune responses , 2004, Nature Immunology.

[104]  Walter Willinger,et al.  Understanding Internet topology: principles, models, and validation , 2005, IEEE/ACM Transactions on Networking.

[105]  G M Edelman,et al.  The evolution of somatic selection: the antibody tale. , 1994, Genetics.

[106]  J. M. Sancho,et al.  Spatiotemporal order out of noise , 2007 .

[107]  Michael Groll Diversity of proteasomal missions: fine tuning of the immune response , 2007 .

[108]  K. Wucherpfennig,et al.  Common themes in the assembly and architecture of activating immune receptors , 2007, Nature Reviews Immunology.

[109]  M Cohn,et al.  The wisdom of hindsight. , 1994, Annual review of immunology.

[110]  B. Beutler,et al.  The interface between innate and adaptive immunity , 2004, Nature Immunology.

[111]  E. Rybicki,et al.  A polymerase chain reaction method adapted for selective amplification and cloning of 3' sequences of potyviral genomes: application to dasheen mosaic virus. , 1993, Journal of virological methods.

[112]  S. Gould,et al.  Exaptation—a Missing Term in the Science of Form , 1982, Paleobiology.

[113]  A. Barabasi,et al.  Global organization of metabolic fluxes in the bacterium Escherichia coli , 2004, Nature.

[114]  Ron Shamir,et al.  Theory and applications , 2004 .

[115]  J. Yewdell,et al.  Immunoproteasomes: regulating the regulator. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[116]  L. Wilkens,et al.  Synchronization of the Noisy Electrosensitive Cells in the Paddlefish , 1999 .

[117]  S. Gould Exaptation: A Crucial Tool for an Evolutionary Psychology , 1991 .

[118]  Hermann-Georg Holzhütter,et al.  Modeling the in vitro 20S proteasome activity: the effect of PA28-alphabeta and of the sequence and length of polypeptides on the degradation kinetics. , 2008, Journal of molecular biology.

[119]  R. Callard,et al.  Immunology and mathematics: crossing the divide , 2005, Immunology.

[120]  L. Pauling,et al.  Molecules as documents of evolutionary history. , 1965, Journal of theoretical biology.

[121]  L. Pauling,et al.  A Theory of the Color of Dyes. , 1939, Proceedings of the National Academy of Sciences of the United States of America.

[122]  G. Edelman,et al.  A measure for brain complexity: relating functional segregation and integration in the nervous system. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[123]  Karl J. Friston,et al.  Degeneracy and redundancy in cognitive anatomy , 2003, Trends in Cognitive Sciences.

[124]  Joachim Kurtz,et al.  Introduction. Ecological immunology , 2009, Philosophical Transactions of the Royal Society B: Biological Sciences.

[125]  Uri Hershberg,et al.  Antigen-receptor degeneracy and immunological paradigms. , 2004, Molecular immunology.

[126]  H. Kitano,et al.  A comprehensive pathway map of epidermal growth factor receptor signaling , 2005, Molecular systems biology.

[127]  Ofer Feinerman,et al.  Quantitative challenges in understanding ligand discrimination by αβ T cells , 2008 .

[128]  Karl J. Friston,et al.  Degenerate neuronal systems sustaining cognitive functions , 2004, Journal of anatomy.

[129]  Edelman Gm,et al.  The evolution of somatic selection: the antibody tale. , 1994 .

[130]  Albert-László Barabási,et al.  Limits of Predictability in Human Mobility , 2010, Science.