Programming with models: Modularity and abstraction provide powerful capabilities for systems biology

Journal of the Royal Society Interface

Volumn 6, Issue 32, 2009, Pages 257-270

  Mallavarapu, Aneil ^a   Thomson, Matthew ^a   Ullian, Benjamin ^a   Gunawardena, Jeremy ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Abstraction; Model building; Modularity; Systems biology

Indexed keywords

ABSTRACTING; BIOLOGY;

ABSTRACTION; BIOLOGICAL PROCESS; COMPUTATIONAL INFRASTRUCTURE; CURRENT CONSTRUCTION; DATATYPES; FUNDAMENTAL BARRIERS; GENERIC PROPERTIES; MODULARITY; SUB-SYSTEMS; SYSTEMS BIOLOGY;

MODEL BUILDINGS;

ARTICLE; BIOLOGY; MATHEMATICAL MODEL; MOLECULAR INTERACTION; MOLECULAR LIBRARY; NONHUMAN; PHENOTYPE; POLARIZATION; PROTEIN PHOSPHORYLATION; SYSTEM ANALYSIS; ANIMAL; BIOLOGICAL MODEL; COMPUTER PROGRAM; DROSOPHILA; METABOLISM; METHODOLOGY; PHOSPHORYLATION; SYSTEMS BIOLOGY;

ANIMALS; DROSOPHILA; MODELS, BIOLOGICAL; PHOSPHORYLATION; SOFTWARE; SYSTEMS BIOLOGY;

EID: 64549144670     PISSN: 17425689     EISSN: 17425662     Source Type: Journal    
DOI: 10.1098/rsif.2008.0205     Document Type: Article

References (79)

1. Aldridge, B. B., Burke, J. M., Lauffenburger, D. A. & Sorger, P. K. 2006 Physicochemical modelling of cell signalling pathways. Nat. Cell Biol. 8, 1195-1203. (doi:10.1038/ncb1497)
2. Alon, U., Surette, M. G., Barkai, N. & Leibler, S. 1999 Robustness in bacterial chemotaxis. Nature 307, 168-171. (doi:10.1038/307168a0) (Pubitemid 29050922)
3. Angeli, D., Ferrell, J. E. & Sontag, E. D. 2004 Detection of multistability, bifurcations, and hysteresis in a large class of biological positive-feedback systems. Proc. Natl Acad. Sci. USA 101, 1822-1827. (doi:10.1073/pnas.0308265100)
4. Arkin, A. P. 2001 Synthetic cell biology. Curr. Opin. Biotechnol. 12, 638-644. (doi:10.1016/S0958-1669(01)00273-7)
5. Aubol, B. E., Chakrabarti, S., Ngo, J., Shaffer, J., Nolen, B., Fu, X.-D., Ghosh, G. & Adams, J. A. 2003 Processive phosphorylation of alternative splicing factor/splicing factor 2. Proc. Natl Acad. Sci. USA 100, 12 601-12 606. (doi:10.1073/pnas.1635129100)
6. Bangs, A. L. & Paterson, T. S. 2003 Finding value in in silico biology. Biosilico 1, 18-22. (doi:10.1016/S1478-5382(03)02218-2)
7. Barbano, P. E., Spivak, M., Flajolet, M., Nairn, A. C., Greengard, P. & Greengard, L. 2007 A mathematical tool for exploring the dynamics of biological networks. Proc. Natl Acad. Sci. USA 104, 19 169-19 174. (doi:10.1073/pnas.0709955104)
8. Becker, S. A., Feist, A. M., Mo, M. L., Hannum, G., Palsson, B. O. & Herrgard, M. J. 2007 Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox. Nat. Protoc. 2, 727-738. (doi:10.1038/nprot.2007.99)
9. Bhalla, U. & Iyengar, R. 1999 Emergent properties of networks of biological signalling pathways. Science 283, 381-387. (doi:10.1126/science.283. 5400.381) (Pubitemid 129501099)
10. Blinov, M. L., Faeder, J. R., Goldstein, B. & Hlavacek, W. S. 2004 BIONETGEN: software for rule-based modeling of signal transduction based on the interactions of molecular domains. Bioinformatics 20, 3289-3291. (doi:10.1093/bioinformatics/bth378) (Pubitemid 39619231)
11. Bower, J. M. & Beeman, D. 1998 The book of GENESIS: exploring realistic neural models with the GEneral NEural SImulation System. New York, NY: Springer.
12. Burack, W. R. & Sturgill, T. W. 1997 The activating dual phosphorylation of MAPK by MEK is nonprocessive. Biochemistry 36, 5929-5933. (doi:10.1021/bi970535d)
13. Carnevale, N. T. & Hines, M. L. 2006 The NEURON book. Cambridge, UK: Cambridge University Press.
14. Ciliberto, A., Capuani, F. & Tyson, J. J. 2007 Modeling networks of coupled enzymatic reactions using the total quasi-steady state approximation. PLoS Comput. Biol. 3, e45. (doi:10.1371/journal.pcbi.0030045) (Pubitemid 46535738)
15. Cohen, P. 1999 The development and therapeutic potential of protein kinase inhibitors. Curr. Opin. Chem. Biol. 3, 459-465. (doi:10.1016/S1367- 5931(99)80067-2)
16. Cohen, P. 2001 The role of reversible protein phosphorylation in health and disease. Eur. J. Biochem. 268, 5001-5010. (doi:10.1046/j.0014-2956.2001. 02473.x)
17. Danos, V. & Laneve, C. 2004 Formal molecular biology. Theor. Comput. Sci. 325, 69-110. (doi:10.1016/j.tcs.2004.03.065)
18. Danos, V., Feret, J., Fontana, W. & Krivine, J. 2007 Scalable simulation of cellular signalling networks. In Proc. APLAS 2007. Lecture Notes in Computer Science, vol.4807. Berlin, Germany: Springer.
19. Danos, V., Feret, J., Fontana, W. & Krivine, J. 2008 Abstract interpretation of cellular signalling networks. In Proc. VMCAI 2008. Lecture Notes in Computer Science, vol.4905. Berlin, Germany: Springer. (Pubitemid 351358216)
20. Ermentrout, B. 2002 Simulating, analyzing, and animating dynamical systems: a guide to Xppaut for researchers and students. Philadelphia, PA: SIAM.
21. Feinberg, M. 1995 The existence and uniqueness of steady states for a class of chemical reaction networks. Arch. Rat. Mech. Anal. 132, 311-370. (doi:10.1007/BF00375614)
22. Ferrell, J. E. & Bhatt, R. R. 1997 Mechanistic studies of the dual phosphorylation of mitogen-activated protein kinase. J. Biol. Chem. 272, 19 008-19 016. (doi:10.1074/jbc.272.30.19008)
23. Fiol, C. J. & Roach, P. J. 1996 Hierarchical phosphorylation of proteins. In Protein phosphorylation (ed. F. Marks). Berlin, Germany: VCH Verlagsgesellschaft.
24. Fisher, J. & Henzinger, T. 2007 Executable cell biology. Nat. Biotechnol. 25, 1239-1249. (doi:10.1038/nbt1356)
25. Forgy, C. L. 1982 Rete: a fast algorithm for the many pattern/many object pattern match problem. Artif. Intell. 19, 17-37. (doi:10.1016/0004-3702(82) 90020-0)
26. Furdui, C. M., Lew, E. D., Schlessinger, J. & Anderson, K. S. 2006 Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reaction. Mol. Cell 21, 711-717. (doi:10.1016/j.molcel.2006.01.022) (Pubitemid 43290737)
27. Gibson, M. C., Patel, A. B., Nagpal, R. & Perrimon, N. 2006 The emergence of geometric order in proliferating metazoan epithelia. Nature 442, 1038-1041. (doi:10.1038/nature05014) (Pubitemid 44330260)
28. Ginkel, A., Kremling, A., Nutsch, T., Rehner, R. & Gilles, E. D. 2003 Modular modelling of cellular systems with ProMot/Diva. Bioinformatics 19, 1169-1176. (doi:10.1093/bioinformatics/btg128) (Pubitemid 36790021)
29. Graham, P. 1996 ANSI common lisp. Series in Artificial Intelligence. Upper Saddle River, NJ: Prentice Hall.
30. Gunawardena, J. 2005 Multisite protein phosphorylation makes a good threshold but can be a poor switch. Proc. Natl Acad. Sci. USA 102, 14 617-14 622. (doi:10.1073/pnas.0507322102)
31. Gutenkunst, R. N., Waterfall, J. J., Casey, F. P., Brown, K. S., Myers, C. R. & Sethna, J. P. 2007 Universally sloppy parameter sensitivities in systems biology models. PLoS Comput. Biol. 3, 1871-1878. (doi:10.1371/journal. pcbi.0030189)
32. Haberichter, T. et al. 2007 A systems biology dynamical model of mammalian G1 cell cycle progression. Mol. Syst. Biol. 3, 84. (doi:10.1038/msb4100126)
33. Hanger, D. P., Byers, H. L., Wray, S., Leung, K. Y., Saxton, M. J., Seereeram, A., Reynolds, C. H., Ward, M. A. & Anderton, B. H. 2007 Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis. J. Biol. Chem. 282, 23 645-23 654. (doi:10.1074/jbc.M703269200)
34. Hartwell, L. H., Hopfield, J. J., Leibler, S. & Murray, A. W. 1999 From molecular to modular cell biology. Nature 402, C47-C52. (doi:10.1038/35011540) (Pubitemid 129516303)
35. Harwood, A. J. 2001 Regulation of GSK-3: a cellular multiprocessor. Cell 105, 821-824. (doi:10.1016/S0092-8674(01)00412-3)
36. Hausmann, S., Erdjument-Bromage, H. & Shuman, S. 2004 Schizosaccharomyces pombe carboxyl-terminal domain (CTD) phosphatase Fcp1: distributive mechanism, minimal CTD substrate and active site mapping. J. Biol. Chem. 209, 10 892-10 900. (doi:10.1074/jbc.M312513200)
37. Hendriks, B. S. et al. 2006 Decreased internalisation of ErbB1 mutants in lung cancer is linked with a mechanism conferring sensitivity to gefitinib. IEE Proc. Syst. Biol. 153, 457-466. (doi:10.1049/ip-syb:20050108)
38. Hlavacek, W. S., Faeder, J. R., Blinov, M. L., Posner, R. G., Hucka, M. & Fontana, W. 2006 Rules for modeling signaltransduction systems. Sci. STKE 344, re6. (doi:10.1126/stke.3442006re6)
39. Holmberg, C. I., Tran, S. E. F., Eriksson, J. E. & Sistonen, L. 2002 Multisite phosphorylation provides sophisticated regulation of transcription factors. Trends Biochem. Sci. 27, 619-627. (doi:10.1016/S0968-0004(02)02207-7)
40. Huang, C.-Y. F. & Ferrell, J. E. 1996 Ultrasensitivity in the mitogen-activated protein kinase cascade. Proc. Natl Acad. Sci. USA 93, 10 078-10 083. (doi:10.1073/pnas.93.19.10078)
41. Hucka, M. et al. 2003 The Systems Biology Markup Language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19, 524-531. (doi:10.1093/bioinformatics/btg015) (Pubitemid 36336519)
42. Ideker, T., Galitski, T. & Hood, L. 2001 A new approach to decoding life: systems biology. Annu. Rev. Genom. Hum. Genet. 2, 343-372. (doi:10.1146/annurev.genom.2.1.343)
43. Ingolia, N. T. 2004 Topology and robustness in the Drosophila segment polarity network. PLoS Biol. 2, 0805-0815. (doi:10.1371/journal.pbio.0020123)
44. Jaqaman, K. & Danuser, G. 2006 Linking data to models: data regression. Nat. Rev. Mol. Cell Biol. 7, 813-819. (doi:10.1038/nrm2030)
45. Jeffrey, D. A., Springer, M., King, D. S. & O'Shea, E. K. 2001 Multi-site phosphorylation of Pho4 by the cyclin-CDK Pho80-Pho85 is semi-processive with site preference. J. Mol. Biol. 306, 997-1010. (doi:10.1006/jmbi.2000.4417)
46. Kirschner, M. 2005 The meaning of systems biology. Cell 121, 503-504. (doi:10.1016/j.cell.2005.05.005) (Pubitemid 40720002)
47. Kitano, H. 2002 Computational systems biology. Nature 420, 206-210. (doi:10.1038/nature01254) (Pubitemid 35340131)
48. Kitano, H., Funahashi, A., Matsuoka, Y. & Oda, K. 2005 Using process diagrams for the graphical representation of biological networks. Nat. Biotechnol. 23, 961-966. (doi:10.1038/nbt1111)
49. Kohn, K. W., Aladjem, M. I., Weinstein, J. N. & Pommier, Y. 2006 Molecular interaction maps of bioregulatory networks: a general rubric for systems biology. Mol. Biol. Cell 17, 1-13. (doi:10.1091/mbc.E05-09-0824)
50. Krummenacker, M., Paley, S., Mueller, L., Yan, T. & Karp, P. D. 2005 Querying and computing with BioCyc databases. Bioinformatics 21, 3454-3455. (doi:10.1093/bioinformatics/bti546) (Pubitemid 41222462)
51. Lawrence, P. A. 1992 The making of a fly. Oxford, UK: Blackwell Science.
52. Levchenko, A., Bruck, J. & Sternberg, P. W. 2000 Scaffold proteins may biphasically affect the levels of mitogenactivated protein kinase signaling and reduce its threshold properties. Proc. Natl Acad. Sci. USA 97, 5818-5823. (doi:10.1073/pnas.97.11.5818)
53. Li, S., Assmann, S. M. & Albert, R. 2006 Predicting essential components of signal transduction networks: a dynamic model of guard cell abscissic acid signaling. PLoS Biol. 4, e312. (doi:10.1371/journal.pbio.0040312) (Pubitemid 44610093)
54. Lloyd, C. M., Halstead, M. D. B. & Nielsen, P. F. 2004 CellML: its future, present and past. Prog. Biophys. Mol. Biol. 85, 433-450. (doi:10.1016/j.pbiomolbio.2004.01.004)
55. Lok, L. & Brent, R. 2005 Automatic generation of cellular reaction networks with MOLECULIZER 1.0. Nat. Biotechnol. 23, 131-136. (doi:10.1038/nbt1054)
56. Longabaugh, W. J. R., Davidson, E. H. & Bolouri, H. 2005 Computational representation of developmental genetic regulatory networks. Dev. Biol. 283, 1-16. (doi:10.1016/j.ydbio.2005.04.023)
57. Massar, J. P., Travers, M., Elhai, J. & Shrager, J. 2005 BIOLINGUA: a programmable knowledge environment for biologists. Bioinformatics 21, 199-207. (doi:10.1093/bioinformatics/bth465) (Pubitemid 40202021)
58. Meier-Schellersheim, M., Xu, X., Angermann, B., Kunkel, E. J., Jin, T. & Germain, R. N. 2006 Key role of local regulation in chemosensing revealed by a new molecular interaction-based modeling method. PloS Comput. Biol. 2, 0710-0724. (doi:10.1371/journal.pcbi.0020082) (Pubitemid 44147382)
59. Meir, E., Munro, E. M., Odell, G. M. & von Dassow, G. 2002 INGENEUE: a versatile tool for reconstituting genetic networks, with examples from the segment polarity network. J. Exp. Zool. Part B 294, 216-251. (doi:10.1002/jez.10187)
60. Morrison, D. K. & Davis, R. J. 2003 Regulation of MAP kinase signalling modules by scaffold proteins in mammals. Annu. Rev. Cell Dev. Biol. 19, 91-118. (doi:10.1146/annurev.cellbio.19.111401.091942)
61. Novére, N. L. et al. 2005 Minimum information requested in the annotation of biochemical models (MIRIAM). Nat. Biotechnol. 23, 1509-1515. (doi:10.1038/nbt1156)
62. Novére, N. L. et al. 2006 Biomodels database: a free, centralized database of curated, published, quantitative kinetic models of biochemical and cellular systems. Nucleic Acids Res. 34, D689-D691. (doi:10.1093/nar/gkj092)
63. Pellicena, P. & Miller, W. T. 2001 Processive phosphorylation of p130Cas by Src depends on SH3-polyproline interactions. J. Biol. Chem. 276, 28 190-28 196. (doi:10.1074/jbc.M100055200)
64. Ramsey, S., Orrell, D. & Bolouri, H. 2005 DIZZY: stochastic simulation of large-scale genetic regulatory networks. J. Bioinform. Comput. Biol. 3, 415-436. (doi:10.1142/S0219720005001132)
65. Rand, D. A., Shulgin, B. V., Salazar, J. D. & Millar, A. J. 2005 Uncovering the design principles of circadian clocks: mathematical analysis of flexibility and evolutionary goals. J. Theor. Biol. 238, 616-635. (doi:10.1016/j.jtbi.2005.06.026)
66. Roach, P. J. 1991 Multisite and hierarchal protein phosphorylation. J. Biol. Chem. 266, 14 139-14 142.
67. Schoeberl, B., Eichler-Jonsson, C., Gilles, E. D. & Müller, G. 2002 Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors. Nat. Biotechnol. 20, 370-375. (doi:10.1038/nbt0402-370)
68. Shapiro, B. E., Levchenko, A., Meyerowitz, E. M., Wold, B. J. & Mjolsness, E. D. 2003 Cellerator: extending a computer algebra system to include biochemical arrows for signal transduction simulations. Bioinformatics 19, 677-678. (doi:10.1093/bioinformatics/btg042) (Pubitemid 36417072)
69. Sinclair, K. H. & Moon, D. A. 1991 The philosophy of Lisp. Commun. ACM 34, 41-47. (doi:10.1145/114669.133119)
70. Slepchenko, B. M., Schaff, J. C., Carson, J. H. & Loew, L. M. 2002 Computational cell biology: spatiotemporal simulation of cellular events. Annu. Rev. Biophys. Biomol. Struct. 31, 423-441. (doi:10.1146/annurev.biophys.31. 101101.140930)
71. Stiles, J. R. & Bartol, T. M. 2001 Monte Carlo methods for simulating realistic synaptic microphysiology using MCell. In Computational neuroscience: realistic modeling for experimentalists (ed. E. de Schutter), pp. 87-127. Boca Raton, FL: CRC Press.
72. Thomson, M. & Gunawardena, J. Submitted. A new method of symbolic parameter analysis reveals unlimited multistability in multisite phosphorylation systems.
73. Velazquez-Dones, A., Hagopian, J. C.,Ma, C.-T., Zhong, X.-Y., Zhou, H., Ghosh, G., Fu, X.-D. & Adams, J. A. 2005 Mass spectrometric and kinetic analysis of ASF/SF2 phosphorylation by SRPK1 and Clk/Sty. J. Biol. Chem. 280, 41 761-41 768. (doi:10.1074/jbc.M504156200)
74. von Dassow, G. & Odell, G. M. 2002 Design and constraints of the Drosophila segment polarity module: robust spatial patterning emerges from intertwined cell state switches. J. Exp. Zool. Part B 294, 179-215. (doi:10.1002/jez.10144)
75. von Dassow, G., Meir, E., Munro, E. M. & Odell, G. M. 2000 The segment polarity network is a robust developmental module. Nature 406, 188-192. (doi:10.1038/35018085) (Pubitemid 30469001)
76. Waas, W. F., Lo, H.-H. & Dalby, K. N. 2001 The kinetic mechanism of the dual phosphorylation of the ATF2 transcription factor by p38 mitogen activated protein (MAP) kinase α. J. Biol. Chem. 278, 5676-5684. (doi:10.1074/jbc.M008787200)
77. Webb, K. & White, T. 2005 UML as a cell and biochemistry modelling language. BioSystems 50, 283-302. (doi:10.1016/j.biosystems.2004.12.003) (Pubitemid 40693501)
78. Wolpert, L. 2001 Principles of development. Oxford, UK: Oxford University Press.
79. Zhao, Y. & Zhang, Z.-Y. 2001 The mechanism of dephosphorylation of extracellular signal-regulated kinase 2 by mitogen-activated protein kinsae phosphatase 3. J. Biol. Chem. 276, 32 382-32 391. (doi:10.1074/jbc.M103369200)