Russian version English version
Volume 8   Issue 1   Year 2013
Akberdin I.R., Kazantsev F.V., Ermak T.V., Timonov V.S., Khlebodarova T.M., Likhoshvai V.A.

In Silico Cell: Challenges and Perspectives

Mathematical Biology & Bioinformatics. 2013;8(1):295-315.

doi: 10.17537/2013.8.295.


  1. Watson JD, Crick FH. Molecular structure ofnucleic acids: A structure for deoxyribose. Nucleic Acid. Nature. 1953;171:737-738.
  2. Jacob F, Monod J. Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol. 1961;3:318-356. doi: 10.1016/S0022-2836(61)80072-7
  3. Palsson B. The challenges of in silico biology. Nat. Biotechnol. 2000;18:1147-1150. doi: 10.1038/81125
  4. Evans GA. Designer science and the “omic” revolution. Nat. Biotechnol. 2000;18:127. doi: 10.1038/72480
  5. Kitano H. Foundations of Systems biology. MIT Press; 2001. 290 p.
  6. Klipp E, Liebermeister W, Wierling C, Kowald A, Lehrach H, Herwig R. Systems Biology: a Textbook. 2009. 592 p.
  7. Tomita M, Hashimoto K, Takahashi K, Shimizu TS, Matsuzaki Y, Miyoshi F, Saito K, Tanida S, Yugi K, Venter JC, Hutchison CA. E-CELL: Software Environment for Whole Cell Simulation. Genome Inform Ser Workshop Genome Inform. 1997;8:147-155.
  8. Karr JR, Sanghvi JC, Macklin DN, Gutschow MV, Jacobs JM, Bolival Jr B, Assad-Garcia N, Glass JI, Covert MW. A whole-cell computational model predicts phenotype from genotype. Cell. 2012;150:389-401. doi: 10.1016/j.cell.2012.05.044
  9. Shuler ML, Foley P, Atlas J. Modeling a minimal cell. Meth. Mol. Biol. 2012;881:573-610. doi: 10.1007/978-1-61779-827-6_20
  10. Gavin T. Escherichia coli: model and menace. Microbiology today. 2004;31:114-115.
  11. Glasner J, Perna N. Comparative genomics of E. coli. Microbiology today. 2004;31:124-125.
  12. Cooper S, Helmstetter CE. Chromosome Replication and the Division Cycle of Escherichia coli B/r. J. Mol. Biol. 1968;31:619-644. doi: 10.1016/0022-2836(68)90425-7
  13. Pritchard RH, Barth PT, Collins J. Control of DNA synthesis in bacteria. Microbial Growth, Symposium of Society of General Microbiology. 1969;19:263-297.
  14. Zaritsky A, Vischer N, Rabinovitch A. Changes of initiation mass and cell dimensions by the 'eclipse'. Mol. Microbiol. 2007;63(1):15-21. doi: 10.1111/j.1365-2958.2006.05501.x
  15. Zaritsky A, Wang P, Vischer NO. Instructive simulation of the bacterial cell division cycle. Microbiology. 2011;157(7):1876-1885. doi: 10.1099/mic.0.049403-0
  16. Drozdov-Tikhomirov LN, Scurida GI, Serganova VV. Inner metabolic fluxes in multienzyme systems: Lysine synthesis on acetate by Clostridium acetobutylicum. Biotechnologia (Moskow). 1986;2:28-37.
  17. Drozdov-Tikhomirov LN, Scurida GI, Davidov AV, Alexandrov AA, Zvyagilskaya RA. Mathematical modeling of living cell metabolism using the method of steady-state stoichiometric flux balance. J. Bioinform. Comput. Biol. 2006;4:865-885. doi: 10.1142/S0219720006002247
  18. Varma A, Palsson BO. Stoichiometric flux balance models quantitatively predict growth and metabolic by-product secretion in wild-type Escherichia coli W3110. Appl. Environ. Microbiol. 1994;60(10):3724-3731.
  19. Nazipova NN, Elkin YuE, Panjukov VV, Drozdov-Tikhomirov LN. Rate Calculation for Metabolic Reactions in a Living and Growing Cell by the Method of Steady-State Stoichiometric Flux Balance. Mathematical Biology and Bioinformatics. 2007;2:98-119 (in Russ.). doi: 10.17537/2007.2.98
  20. Llaneras F, Pico J. Stoichiometric modeling of cell metabolism. J. Biosci. Bioeng. 2008;105:1-11. doi: 10.1263/jbb.105.1
  21. Edwards JS, Palsson BO. The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities. PNAS. 2000;97(10):5528-5533. doi: 10.1073/pnas.97.10.5528
  22. Reed JL, Palsson BO. Thirteen Years of Building Constraints-Based in silico Models of Escherichia coli. J. Bacteriol. 2003;185(9):2692-2699. doi: 10.1128/JB.185.9.2692-2699.2003
  23. Kim JI, Varner JD, Ramkrishna D. A hybrid model of anaerobic E. coli GJT001: combination of elementary flux modes and cybernetic variables. Biotechnol. Prog. 2008;24(5):993-1006. doi: 10.1002/btpr.73
  24. Covert MW, Xiao N, Chen TJ, Karr JR. Integrating metabolic, transcriptional regulatory and signal transduction models in Escherichia coli. Bioinformatics. 2008;24(18):2044-2050. doi: 10.1093/bioinformatics/btn352. doi: 10.1093/bioinformatics/btn352
  25. Edwards JS, Ibarra RU, Palsson BO. In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data. Nat. Biotechnol. 2001;19:125-130. doi: 10.1038/84379
  26. Van Dien SJ, Iwatani S, Usuda Y, Matsui K. Theoretical analysis of amino acid-producing Escherichia coli using a stoichiometric model and multivariate linear regression. J. Biosci. Bioeng. 2006;102:34-40. doi: 10.1263/jbb.102.34
  27. Shuler ML, Leung S, Dick CC. A mathematical model for the growth of a single bacterial cell. Ann. N. Y. Acad. Sci. 1979;326(1):35-52. doi: 10.1111/j.1749-6632.1979.tb14150.x
  28. Domach MM, Leung SK, Cahn RE, Cocks GG, Shuler ML. Computer-model for glucose-limited growth of a single cell of Escherichia coli b/R-A. Biotechnol. Bioeng. 1984;26:203-216. doi: 10.1002/bit.260260303
  29. Shuler ML. Single-cell models: Promise and limitations. J. Biotechnol. 1999;71:225-228. doi: 10.1016/S0168-1656(99)00024-3
  30. Browning ST, Shuler ML. Towards the development of a minimal cell model by generalization of a model of Escherichia coli: Use of dimensionless rate parameters. Biotechnol. Bioeng. 2001;76:187-192. doi: 10.1002/bit.10007
  31. Browning ST, Castellanos M, Shuler ML. Robust control of initiation of prokaryotic chromosome replication: essential considerations for a minimal cell. Biotechnol. Bioeng. 2004;88(5):575-584. doi: 10.1002/bit.20223
  32. Peterson SN, Hu PC, Bott KF, Hutchison CA. 3rd. A survey of the Mycoplasma genitalium genome by using random sequencing. J. Bacteriol. 1993;175(24):7918-7930.
  33. Holden C. Cell biology. Alliance launched to model E. coli. Science. 2002;297(5586):1459-1460. doi: 10.1126/science.297.5586.1459a
  34. Snoep JL. The Silicon Cell initiative: working towards a detailed kinetic description at the cellular level. Curr. Opin. Biotechnol. 2005;16(3):336-343. doi: 10.1016/j.copbio.2005.05.003
  35. Ruckenstein E, Simon Z. Regulation and synthesis in the living cell. I. Kinetics of ribonucleic acid synthesis. J. Theor. Biol. 1966;11(2):282-298. doi: 10.1016/0022-5193(66)90166-4
  36. Tchuraev RN, Ratner VA. Modelling of the Molecular Genetic Systems of Control by Means of Automata Theory Language. I. Operons and Operon Systems. In: Issledovaniia po teoreticheskoi genetike (Studies on theoretical genetics). Novosibirsk; 1972. P. 210-228 (in Russ.).
  37. Likhoshvai VA, Matushkin YuG, Vatolin YuN, Bazhan SI. A generalized chemical kinetic method for simulating complex biological systems. A computer model of λ phage ontogenesis. Comput. Technol. 2000;5(2):87-99.
  38. Covert MW, Knight EM, Reed JL, Herrgard MJ, Palsson BO. Integrating high-throughput and computational data elucidates bacterial networks. Nature. 2004;429:92-96. doi: 10.1038/nature02456
  39. Thiele I, Jamshidi N, Fleming RM, Palsson BO. Genome scale reconstruction of Escherichia coli’s transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization. PLoS Comput. Biol. 2009;5(3):e1000312. doi: 10.1371/journal.pcbi.1000312. doi: 10.1371/journal.pcbi.1000312
  40. Orth JD, Conrad TM, Na J, Lerman JA, Nam H, Feist AM, Palsson BO. A comprehensive genome-scale reconstruction of Escherichia coli metabolism-2011. Mol. Syst. Biol. 2011;7:535. doi: 10.1038/msb.2011.65
  41. Glass L. Combinatorial and topological methods in nonlinear chemical kinetics. J. Chem. Phys. 1975;63(4):1325-1335. doi: 10.1063/1.431518
  42. Edwards R. Analysis of continuous-time switching networks. Physica D. 2000;146:165-199. doi: 10.1016/S0167-2789(00)00130-5
  43. Kauffman S. Metabolic stability and epigenesis in randomly constructed genetic net. J. Theor. Biol. 1969;22(3):437-467. doi: 10.1016/0022-5193(69)90015-0
  44. Thomas R. Boolean formalization of genetic control circuits. J. Theor. Biol. 1973;42(3):563-585. doi: 10.1016/0022-5193(73)90247-6
  45. Mestl T, Plahte E, Omholt SW. A mathematical framework for describing and analysing gene regulatory networks. J. Theor. Biol. 1995;176(2):291-300. doi: 10.1006/jtbi.1995.0199
  46. Endy D, Kong D, Yin J. Intracellular kinetics of a growing virus: a genetically structured simulation for bacteriophage T7. Biotechnol. Bioeng. 1997;55(2):375-389. doi: 10.1002/(SICI)1097-0290(19970720)55:2<375::AID-BIT15>3.0.CO;2-G
  47. Smolen P, Baxter DA, Byrne JH. Modeling transcriptional control in gene networks - methods, recent results, and future directions. Bull. Math. Biol. 2000;62(2):247-292. doi: 10.1006/bulm.1999.0155
  48. Covert MW, Palsson BO. Constraints-based models: regulation of gene expression reduces the steady-state solution space. J. Theor. Biol. 2003;221(3):309-325. doi: 10.1006/jtbi.2003.3071
  49. Gillespie D. Exact stochastic simulation of coupled chemical reactions. J. Phys. Chem. 1977;81:2340-2361. doi: 10.1021/j100540a008
  50. McAdams HH, Arkin A. Stochastic mechanisms in gene expression. Proc. Nat. Acad. Sci. USA. 1997;94(3):814-819. doi: 10.1073/pnas.94.3.814
  51. Ianenko NN. Metod drobnykh shagov dlia resheniia mnogomernykh zadach matematicheskoi fiziki (The method of fractional steps for solution of problems of mathematical physics). Novosibirsk; 1967. 167 p. (in Russ.).
  52. Gear CW. The automatic integration of ordinary differential equations. Communs. ACM. 1971;14:176-190. doi: 10.1145/362566.362571
  53. Butcher JC. Numerical methods for ordinary differential equations. Wiley; 2008. doi: 10.1002/9780470753767
  54. Elowitz MB, Levine AJ, Siggia ED, Swain PS. Stochastic gene expression in a single cell. Science. 2002;297:1183-1186. doi: 10.1126/science.1070919
  55. Berthoumieux S, de Jong H, Baptist G, Pinel C, Ranquet C, Ropers D, Geiselmann J. Shared control of gene expression in bacteria by transcription factors and global physiology of the cell. Mol. Syst. Biol. 2013;9:634. doi:10.1038/msb.2012.70. doi: 10.1038/msb.2012.70
  56. Dennis P, Ehrenberg M, Bremer H. Control of rRNA synthesis in Escherichia coli: a systems biology approach. Microbiol. Mol. Biol. Rev. 2004;68:639-668. doi: 10.1128/MMBR.68.4.639-668.2004
  57. Maaloe O, Kjeldgaard NO. Control of macromolecular synthesis: a study of DNA, RNA, and protein synthesis in bacteria. New York: WA Benjamin; 1966. V. 4.
  58. Scott M, Hwa T. Bacterial growth laws and their applications. Curr. Opin. Biotechnol. 2011;22(4):559-565. doi: 10.1016/j.copbio.2011.04.014
  59. Sundararaj S, Guo A, Habibi-Nazhad B, Rouani M, Stothard P, Ellison M, Wishart DS. The CyberCell Database (CCDB): a comprehensive, self-updating, relational database to coordinate and facilitate in silico modeling of Escherichia coli. Nucl. Acids Res. 2004;32:D293-D295. doi: 10.1093/nar/gkh108
  60. Schulz M, Krause F, Le Novere N, Klipp E, Liebermeister W. Retrieval, alignment, and clustering of computational models based on semantic annotations. Mol. Syst. Biol. 2011;7:512. doi:10.1038/msb.2011.41. doi: 10.1038/msb.2011.41
  61. Courtot M, Juty N, Knupfer C, Waltemath D, Zhukova A, Dräger A, Dumontier M, Finney A, Golebiewski M, Hastings J et al. Controlled vocabularies and semantics in systems biology. Mol. Syst. Biol. 2011;7:543. doi:10.1038/msb.2011.77. doi: 10.1038/msb.2011.77
  62. Blattner FR, Plunkett G III, Bloch C, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF et al. The complete genome sequence of Escherichia coli K-12. Science. 1997;277(5331):1453-1462. doi: 10.1126/science.277.5331.1453
  63. C. elegans Sequencing Consortium. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998;282(5396):2012-2018. doi: 10.1126/science.282.5396.2012
  64. Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA, Galle RF et al. The genome sequence of Drosophila melanogaster. Science. 2000;287(5461):2185-2195. doi: 10.1126/science.287.5461.2185
  65. Bakstad D, Adamson A, Spiller DG, White MRH. Quantitative measurement of single cell dynamics. Curr. Opin. Biotechnol. 2012;23:103-109. doi: 10.1016/j.copbio.2011.11.007
  66. Dubuis JO, Samanta R, Gregor T. Accurate measurements of dynamics and reproducibility in small genetic networks. Mol. Syst. Biol. 2013;9:639. doi: 10.1038/msb.2012.72. doi: 10.1038/msb.2012.72
  67. Hanley MB, Lomas W, Mittar D, Maino V, Park E. Detection of Low Abundance RNA Molecules in Individual Cells by Flow Cytometry. PLoS ONE. 2013;8(2):e57002. doi:10.1371/journal.pone.0057002. doi: 10.1371/journal.pone.0057002
  68. Elowitz MB, Leibler S. A synthetic oscillatory network of transcriptional regulators. Nature. 2000;403(6767):335-338. doi: 10.1038/35002125
  69. Kauffman SA. The origins of order: self-organization and selection in evolution. N.Y.: Oxford Univ. Press; 1993. 223 p.
  70. Graudenzi A, Serra R, Villani M, Damiani C, Colacci A, Kauffman SA. Dynamical properties of a Boolean model of gene regulatory network with memory. J. Comput Biol. 2011;18(10):1291-1303. doi: 10.1089/cmb.2010.0069
  71. Thomas R, Thieffry D, Kaufman M. Dynamical behavior of biological regulatory networks--I. Biological role of feedback loops and practical use of the concept of the loop-characteristic state. Bull. Math. Biol. 1995;57(2):247-276. doi: 10.1007/BF02460618
  72. Thieffry D, Thomas R. Qualitative analysis of gene networks. Pac. Symp. Biocomput. 1998:77-88.
  73. Friedman N, Linial M, Nachman I, Peer D. Using Bayesian networks to analyze expression data. J. Comput. Biol. 2000;7:601-620. doi: 10.1089/106652700750050961
  74. Ong IM, Glasner JD, Page D. Modelling regulatory pathways in E. coli from time series expression profiles. Bioinformatics. 2002;18(1):241-248. doi: 10.1093/bioinformatics/18.suppl_1.S241
  75. Perrin BE, Ralaivola L, Mazurie A, Bottani S, Mallet J, d’Alche-Buc F. Gene networks inference using dynamic Bayesian networks. Bioinformatics. 2003(2):138-148. doi: 10.1093/bioinformatics/btg1071
  76. Hofestadt R, Meineke F. Interactive modelling and simulation of biochemical networks. Comput. Biol. Med. 1995;25(3):321-334. doi: 10.1016/0010-4825(95)00019-Z
  77. Soliman S. Invariants and Other Structural Properties of Biochemical Models as a Constraint Satisfaction Problem. Algorithms Mol. Biol. 2012;7(1):15. doi: 10.1186/1748-7188-7-15
  78. Bazhan SI, Likhoshvay VA, Belova OE. Theoretical analysis of the regulation of interferon expression during priming and blocking. J. Theor. Biol. 1995;175:149-160. doi: 10.1006/jtbi.1995.0127
  79. Likhoshvai VA, Matushkin YuG, Fadeev SI. Problems in the theory of the functioning of genetic networks. Sib. Zh. Ind. Mat. 2003;6(2):64-80 (in Russ.).
  80. Likhoshvai VA, Fadeev SI, Demidenko GV, Matushkin YuG. Modeling nonbranching multistage synthesis by an equation with retarded argument. Sib. Zh. Ind. Mat. 2004;7(1):73-94 (in Russ.).
  81. Demidenko GV, Fadeev SI, Likhoshvai VA, Matushkin YuG, Kolchanov NA. Mathematical simulation of regulatory circuits of gene networks. Computational Mathematics and Mathematical Physics. 2004;44(12):2166-2183.
  82. McAdams H, Arkin A. Simulation of prokaryotic genetic circuits. Ann. Rev. Biophys. Biomed. Struct. 1998;27:199-224. doi: 10.1146/annurev.biophys.27.1.199
  83. Turner TE, Schnell S, Burrage K. Stochastic approaches for modelling in vivo reactions. Comput. Biol. Chem. 2004;28(3):165-178. doi: 10.1016/j.compbiolchem.2004.05.001
  84. Ocone A, Millar AJ, Sanguinetti G. Hybrid regulatory models: a statistically tractable approach to model regulatory network dynamics. Bioinformatics. 2013. doi: 10.1093/bioinformatics/btt069. doi: 10.1093/bioinformatics/btt069
  85. Funahashi A, Morohashi M, Kitano H, Tanimura N. CellDesigner: a process diagram editor for gene-regulatory and biochemical networks. Biosilico. 2003;1(5):159-162. doi: 10.1016/S1478-5382(03)02370-9
  86. Gizzatkulov NM, Goryanin II, Metelkin EA, Mogilevskaya EA, Peskov KV, Demin OV. DBSolve Optimum: a software package for kinetic modeling which allows dynamic visualization of simulation results. BMC Syst. Biol. 2010;4(109):1-11. doi: 10.1186/1752-0509-4-109
  87. Moraru II, Schaff JC, Slepchenko BM, Loew LM. The virtual cell. Ann. N. Y. Acad. Sci. 2002;971(1):595-596. doi: 10.1111/j.1749-6632.2002.tb04535.x
  88. Shapiro BE, Levchenko A, Meyerowitz EM, Wold BJ, Mjolsness ED. Cellerator: extending a computer algebra systems to include biochemical arrows for signal transduction simulations. Bioinformatics. 2003;19(5):677-678. doi: 10.1093/bioinformatics/btg042
  89. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome research. 2003;13(11):2498-2504. doi: 10.1101/gr.1239303
  90. Wegner K, Knabe J, Robinson M, Egri-Nagy A, Schilstra M, Nehaniv C. The NetBuilder'project: development of a tool for constructing, simulating, evolving, and analysing complex regulatory networks. BMC Syst. Biol. 2007;1(1):72. doi: 10.1186/1752-0509-1-S1-P72
  91. Lee DY, Yun C, Cho A, Hou BK, Park S, Lee SY. WebCell: a web-based environment for kinetic modeling and dynamic simulation of cellular networks. Bioinformatics. 2006;22(9):1150-1151. doi: 10.1093/bioinformatics/btl091
  92. Hucka M, Finney A, Sauro HM, Bolouri H, Doyle JC, Kitano H, Arkin AP, Bornstein BJ, Bray D, Cornish-Bowden A et al. The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics. 2003;19(4):524-531. doi: 10.1093/bioinformatics/btg015
  93. Drager A, Hassis N, Supper J, Schroder A, Zell A. SBMLsqueezer: a CellDesigner plug-in to generate kinetic rate equations for biochemical networks. BMC Syst. Biol. 2008;2(1):39. doi: 10.1186/1752-0509-2-39
  94. Wrzodek C, Buchel F, Ruff M, Drager A, Zell A. Precise generation of systems biology models from KEGG pathways. BMC Syst. Biol. 2013;7(1):15. doi: 10.1186/1752-0509-7-15
  95. Takizawa H, Nakamura K, Tabira A, Chikahara Y, Matsui T, Hiroi N, Funahashi A. LibSBMLSim: A reference implementation of fully functional SBML simulator. Bioinformatics. 2013. doi: 10.1093/bioinformatics/btt157. doi: 10.1093/bioinformatics/btt157
  96. Calzone L, Fages F, Soliman S. BIOCHAM: an environment for modeling biological systems and formalizing experimental knowledge. Bioinformatics. 2006;22(14):1805-1807. doi: 10.1093/bioinformatics/btl172
  97. Adams R, Clark A, Yamaguchi A, Hanlon N, Tsorman N, Ali S, Lebedeva G, Goltsov A, Sorokin A, Akman OE et al. SBSI: an extensible distributed software infrastructure for parameter estimation in systems biology. Bioinformatics. 2013;29:664-665. doi: 10.1093/bioinformatics/btt023
  98. Sutterlin T, Kolb C, Dickhaus H, Jager D, Grabe N. Bridging the scales: semantic integration of quantitative SBML in graphical multi-cellular models and simulations with EPISIM and COPASI. Bioinformatics. 2013;29(2):223-229. doi: 10.1093/bioinformatics/bts659
  99. Berkhout J, Teusink B, Bruggeman FJ. Gene network requirements for regulation of metabolic gene expression to a desired state. Sci. Rep. 2013;3:1417. doi:10.1038/srep01417. doi: 10.1038/srep01417
  100. Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI et al. BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst.Biol. 2010;4:92. doi: 10.1186/1752-0509-4-92
  101. Lloyd CM, Lawson JR, Hunter PJ, Nielsen PF. The CellML Model Repository. Bioinformatics. 2008;24(18):2122-2123. doi: 10.1093/bioinformatics/btn390
  102. Olivier BG, Snoep JL. Web-based kinetic modelling using JWS Online. Bioinformatics. 2004;20:2143-2144. doi: 10.1093/bioinformatics/bth200
  103. Sivakumaran S, Hariharaputran S, Mishra J, Bhalla US. The Database of Quantitative Cellular Signaling: management and analysis of chemical kinetic models of signaling networks. Bioinformatics. 2003;19:408-415. doi: 10.1093/bioinformatics/btf860
  104. Moutselos K, Kanaris I, Chatziioannou A, Maglogiannis I, Kolisis FN. KEGGconverter: a tool for the in-silico modelling of metabolic networks of the KEGG Pathways database. BMC Bioinformatics. 2009;10:324. doi: 10.1186/1471-2105-10-324
  105. Rojas I, Golebiewski M, Kania R, Krebs O, Mir S, Weidemann A, Wittig U. SABIO-RK: a database for biochemical reactions and their kinetics. BMC Syst. Biol. 2007;1:S6. doi: 10.1186/1752-0509-1-S1-S6
  106. Forster AC, Church GM. Towards synthesis of a minimal cell. Mol. Syst. Biol. 2006;2(1). doi:10.1038/msb4100090. doi: 10.1038/msb4100090
  107. Stano P. Advances in minimal cell models: A new approach to synthetic biology and origin of life. In: Progress in Molecular and Environmental Bioengineering - From Analysis and Modeling to Technology Applications. Ed. A. Rijeka, Croatia: Carpi. Intech - Open Access Publisher; 2011. P. 23-44.
  108. Noble D. Modeling the heart from genes to cells to the whole organ. Sci. Signal. 2002;295(5560):1678. doi: 10.1126/science.1069881
  109. Lewis NE, Schramm G, Bordbar A, Schellenberger J, Andersen MP, Cheng JK, Patel N, Yee A, Lewis RA, Eils R, König R, Palsson BØ. Formulating multicellular models of metabolism in tissues: application to energy metabolism in the human brain. Nat. Biotechnol. 2010;28(12):1279. doi: 10.1038/nbt.1711
  110. Gardner TS, Cantor CR, Collins JJ. Construction of a genetic toggle switch in Escherichia coli. Nature. 2000;403(6767):339-342. doi: 10.1038/35002131
  111. Tchuraev RN, Stupak IV, Tropynina TS, Stupak EE. Epigenes: design and construction of new hereditary units. FEBS letters. 2000;486(3):200. doi: 10.1016/S0014-5793(00)02300-0
  112. Hasty J, Dolnik M, Rottschafer V, Collins JJ. Synthetic gene network for entraining and amplifying cellular oscillations. Phys. Rev. Letters. 2002;88(14):148101. doi: 10.1103/PhysRevLett.88.148101
  113. Atkinson MR, Savageau MA, Myers JT, Ninfa AJ. Development of Genetic Circuitry Exhibiting Toggle Switch or oscillatory behavior in Escherichia coli. Cell. 2003;113(5):597-607. doi: 10.1016/S0092-8674(03)00346-5
  114. Feng XJ, Hooshangi S, Chen D, Li G, Weiss R, Rabitz H. Optimizing genetic circuits by global sensitivity analysis. Biophys. J. 2004;87(4):2195-2202. doi: 10.1529/biophysj.104.044131
  115. Golubyatnikov V, Likhoshvai V, Fadeev S, Matushkin Yu, Ratushny A, Kolchanov N. Mathematical and Computer modeling of genetic networks. In: Proceedings of the 6-th International Conference Human and Computer (HC-2003). Japan: University of Aizu; 2003. P. 200-205.
  116. Reich JG, Sel’kov EE. Mathematical analysis of metabolic networks. FEBS Letters. 1974;40:S119-S127. doi: 10.1016/0014-5793(74)80694-0
  117. Ivanitskii G.R., Krinskii V.I., Sel'kov E.E. Matematicheskaia biofizika kletki (Mathematical Biophysics of Cell). Moscow; 1978. 156 p. (in Russ.).
  118. Sel’kov E. On the mechanism of single-frequency self-oscillations in glycolysis. I. A simple kinetic model. Eur. J. Biochem. 1968;4(1):79-86. doi: 10.1111/j.1432-1033.1968.tb00175.x
  119. Shevelev EL, Sel’kov EE. Concentration hierarchy in the mathematical model of fructose-2,6-bisphosphate exchange. Mol. Biol. 1988;22(2):459-465.
  120. Popova SV, Sel'kov EE. Molekuliarnaia biologiia (Molecular Biology). 1978;12:1139-1151 (in Russ.).
  121. Sel’kov E, Basmanova S, Gaasterland T, Goryanin I, Gretchkin Y, Maltsev N, Nenashev V, Overbeek R, Panyushkina E, Pronevitch L, Selkov Jr E, Yunus I. The Metabolic Pathway Collection from EMP: The Enzymes and Metabolic Pathways Database. Nucl. Acids Res. 1996;24(1):26-28. doi: 10.1093/nar/24.1.26
  122. Sel’kov EJr, Grechkin Y, Mikhailova N, Sel’kov E. MPW: the Metabolic Pathways Database. Nucl. Acids Res. 1998;26(1):43-45. doi: 10.1093/nar/26.1.43
  123. Demin OV, Goryanin II, Dronov S, Lebedeva GV. Kinetic model of imidazologlycerol-phosphate synthetase from Escherichia coli. Biochemistry (Mosc). 2004;69(12):1324-1335. doi: 10.1007/s10541-005-0077-4
  124. Demin OV, Plyusnina TY, Lebedeva GV, Zobova EA, Metelkin EA, Kolupaev AG, Goryanin II, Tobin F. Kinetic modelling of the E. coli metabolism. In: Systems Biology. Berlin Heidelberg: Springer; 2005. P. 31-67. doi: 10.1007/4735_85
  125. Peskov K, Goryanin I, Prank K, Tobin F, Demin O. Kinetic modeling of ace operon genetic regulation in Escherichia coli. J. Bioinform. Comput. Biol. 2008;5:933-959. doi: 10.1142/S0219720008003771
  126. Peskov K, Mogilevskaya E, Demin O. Kinetic modelling of central carbon metabolism in Escherichia coli. FEBS J. 2012;279(18):3374-3385. doi: 10.1111/j.1742-4658.2012.08719.x
  127. Metelkin EA, Lebedeva GV, Demin OV, Goryanin II. A kinetic model of Escherichia coli β-galactosidase. Biophysics. 2009;54(2):156-162. doi: 10.1134/S0006350909020067
  128. Ratner VA. Geneticheskie sistemy upravleniia (Genetic Regulatory Systems). Novosibirsk; 1966 (in Russ.).
  129. Belova OE, Likhoshvai VA, Bazhan SI, Kulichkov VA. Computer system for investigation and integrated description of molecular-genetic system regulation of interferon induction and action. Comput. Appl. Biosci. 1995;11(2):213-218.
  130. Ratushnyi AV, Likhoshvai VA, Ignat’eva EV, Matushkin YuG, Goryanin II, Kolchanov NA. Computer Model of a Gene Network on Cholesterol Biosinthesis Regulation in Cell: Analysis of the Impact of Mutations. . . . 2003;389(2):259-262.
  131. Akberdin IR, Ozonov EA, Mironova VV, Omelyanchuk NA, Likhoshvai VA, Gorpinchenko DN, Kolchanov NA. A cellular automation to model the development of primary shoot meristems of Arabidopsis thaliana. J. Bioinform. Comput. Biol. 2007;5(2b):641-650. doi: 10.1142/S0219720007002862
  132. Oshchepkova-Nedosekina EA, Likhoshvai VA. A mathematical model for the adenylosuccinate synthetase reaction involved in purine biosynthesis. Theor. Biol. Med. Model. 2007;4:11. doi: 10.1186/1742-4682-4-11
  133. Akberdin IR, Kazantsev FV, Omelyanchuk NA, Likhoshvai VA. Mathematical model of auxin metabolism in meristem cells of plant shoots. Vavilovskii zhurnal genetiki i selektsii (Russian Journal of Genetics). 2009;13:170-176 (in Russ.).
  134. Mironova VV, Omelyanchuk NA, Yosiphon G, Fadeev SI, Kolchanov NA, Mjolsness E, Likhoshvai VA. How acropetal auxin flow determines cell fate specification along the central axis in root development. BMC Syst. Biol. 2010;4:98. doi: 10.1186/1752-0509-4-98
  135. Likhoshvai VA, Khlebodarova TM. Coordination of Cell Growth and DNA Replication: A Mathematical Model. Mathematical Biology and Bioinformatics. 2013;8(1):66-92. doi: 10.17537/2013.8.66
  136. Khlebodarova TM, Kogai VV, Akberdin IR, Ri NA, Fadeev SI, Likhoshvai VA. Modeling of Nitrite Utilization in E. coli Cells: Flux Analysis. Mathematical Biology and Bioinformatics. 2013;8(1):268-286. doi: 10.17537/2013.8.268
  137. Churaev RN, Ratner VA. In: Issledovaniia po teoreticheskoi genetike (Studies on theoretical genetics). Novosibirsk; 1975. P. 5-66 (in Russ.).
  138. Likhoshvai VA, Matushkin YuG, Fadeev SI. Relationship between a gene network graph and qualitative modes of its functioning. Molecular Biology. 2001;35(6):926-932. doi: 10.1023/A:1013206906557
  139. Likhoshvai V, Ratushny A. Generalized Hill function method for modeling molecular processes. J. Bioinform. Comput. Biol. 2007;5(2):521-531. doi: 10.1142/S0219720007002837
  140. Ratushnyi AV, Likhoshvai VA, Anan'ko EA, Vladimirov NV, Gunbin KV, Lashin SA, Nedosekina EA, Nikolaev SV, Omel'ianchuk LV, Matushkin IuG, Kolchanov NA. Vestnik VOGiS (Russian journal of genetics). 2005;9(2):232-261 (in Russ.).
  141. Likhoshvai VA, Kazantsev FV, Akberdin IR, Bezmaternykh KD. Programma avtomaticheskoi generatsii matematicheskikh modelei gennykh setei (MGSgenerator) (The tool for automatic generation of gene network's mathematical models): Computer software copyright registration certificate 2008611941, 2008 (in Russ.).
  142. Kazantsev FV, Akberdin IR, Bezmaternykh KD, Likhoshvai VA. The tool for automatic generation of gene network's mathematical models. Vavilovskii zhurnal genetiki i selektsii (Russian journal of genetics). 2009;13(1):163-170 (in Russ.).
  143. Likhoshvai VA, Kazantsev FV, Akberdin IR, Bezmaternykh KD, Lashin SA, Podkolodnaia NN, Ratushnyi AV. Komp'iuternaia sistema dlia konstruirovaniia, rascheta i analiza modelei molekuliarno-geneticheskikh sistem (MGSmodeller) (A computer system for the design, calculation and analysis of molecular genetic systems): Computer software copyright registration certificate 2008612820, 2008 (in Russ.).
  144. Ananko EA, Podkolodny NL, Stepanenko IL, Podkolodnaya OA, Rasskazov DA, Miginsky DS, Likhoshvai VA, Ratushny AV, Podkolodnaya NN, Kolchanov NA. GeneNet in 2005. Nucl. Acids Res. 2005;1(33):425-427.
  145. Lakhno V, Nazipova N, Kim V, Filippov S, Zaitsev A, Fialko N, Tyulbasheva G, Ustinin D, Teplukhin A, Ustinin M. Integrated Mathematical Model of the Living Cell. Mathematical Biology and Bioinformatics. 2007;2(2):361-376. doi: 10.17537/2007.2.361
Table of Contents Original Article
Math. Biol. Bioinf.
doi: 10.17537/2013.8.295
published in Russian

Abstract (rus.)
Abstract (eng.)
Full text (rus., pdf)


  Copyright IMPB RAS © 2005-2022