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SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools

Claudine Chaouiya, Duncan Bérenguier, Sarah M Keating and 21 more

BMC Systems Biology · 2013

doi:10.1186/1752-0509-7-135

Abstract

Background. Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing.

Results. We present the Systems Biology Markup Language (SBML) Qualitative Models Package (“qual”), an extension of the SBML Level 3 standard designed for computer representation of qualitative models of biological networks. We demonstrate the interoperability of models via SBML qual through the analysis of a specific signalling network by three independent software tools. Furthermore, the collective effort to define the SBML qual format paved the way for the development of LogicalModel, an open-source model library, which will facilitate the adoption of the format as well as the collaborative development of algorithms to analyse qualitative models.

Conclusions. SBML qual allows the exchange of qualitative models among a number of complementary software tools. SBML qual has the potential to promote collaborative work on the development of novel computational approaches, as well as on the specification and the analysis of comprehensive qualitative models of regulatory and signalling networks.

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References 87

  1. 1.

    Kauffman S Homeostasis and differentiation in random genetic control networksNature1969 71778

    Not in our library10.1038/224177a0

  2. 2.

    Thomas R Boolean formalisation of genetic control circuitsJ Theor Biol1973 7565583

    Not in our library10.1016/0022-5193(73)90247-6

  3. 3.

    Silva-Rocha R de Lorenzo V The TOL network of Pseudomonas putida mt-2 processes multiple environmental inputs into a narrow response spaceEnviron Microbiol2013 727186

    Not in our library10.1111/1462-2920.12014

  4. 4.

    Herrmann F Groß A Zhou D Kestler HA Kühl M A boolean model of the cardiac gene regulatory network determining first and second heart field identityPLoS One2012 7e46798

    Not in our library10.1371/journal.pone.0046798

  5. 5.

    Akman OE Watterson S Parton A Binns N Millar AJ Ghazal P Digital clocks: simple Boolean models can quantitatively describe circadian systemsJ R Soc Interface2012 7236582

    Not in our library10.1098/rsif.2012.0080

  6. 6.

    Giacomantonio CE Goodhill GJ A Boolean model of the gene regulatory network underlying mammalian cortical area developmentPLoS Comput Biol2010 7e1000936

    Not in our library10.1371/journal.pcbi.1000936

  7. 7.

    Tokar T Turcan Z Ulicny J Boolean network-based model of the Bcl-2 family mediated MOMP regulationTheor Biol Med Model2013 740

    Not in our library10.1186/1742-4682-10-40

  8. 8.

    Sridharan S Layek R Datta A Venkatraj J Boolean modeling and fault diagnosis in oxidative stress responseBMC Genomics2012 7Suppl 6S4

    Not in our library10.1186/1471-2164-13-s6-s4

  9. 9.

    Domedel-Puig N Rué P Pons AJ García-Ojalvo J Information routing driven by background chatter in a signaling networkPLoS Comput Biol2011 7e1002297

    Not in our library10.1371/journal.pcbi.1002297

  10. 10.

    Saadatpour A Albert I Albert R Attractor analysis of asynchronous Boolean models of signal transduction networksJ Theor Biol2010 764156

    Not in our library10.1016/j.jtbi.2010.07.022

  11. 11.

    Naldi A Carneiro J Chaouiya C Thieffry D Diversity and plasticity of Th cell types predicted from regulatory network modellingPLoS Comput Biol2010 7e1000912

    Not in our library10.1371/journal.pcbi.1000912

  12. 12.
  13. 13.
  14. 14.

    Helikar T Konvalina J Heidel J Rogers JA Emergent decision-making in biological signal transduction networksProc Natl Acad Sci U S A2008 719131918

    Not in our library10.1073/pnas.0705088105

  15. 15.

    Fauré A Naldi A Chaouiya C Thieffry D Dynamical analysis of a generic Boolean model for the control of the mammalian cell cycleBioinformatics2006 7e12431

    Not in our library10.1093/bioinformatics/btl210

  16. 16.
  17. 17.

    Todd RG Helikar T Ergodic sets as cell phenotype of budding yeast cell cyclePLoS One2012 7e45780

    Not in our library10.1371/journal.pone.0045780

  18. 18.
  19. 19.

    Madrahimov A Helikar T Kowal B Lu G Rogers J Dynamics of influenza virus and human host interactions during infection and replication cycleBull Math Biol2013 79881011

    Not in our library10.1007/s11538-012-9777-2

  20. 20.

    Feuer R Gottlieb K Viertel G Klotz J Schober S Bossert M Sawodny O Sprenger G Ederer M Model-based analysis of an adaptive evolution experiment with Escherichia coli in a pyruvate limited continuous culture with glycerolEURASIP J Bioinform Syst Biol2012 714

    Not in our library10.1186/1687-4153-2012-14

  21. 21.
  22. 22.

    Li F Long T Lu Y Ouyang Q Tang C The yeast cell-cycle network is robustly designedProc Natl Acad Sci U S A2004 747816

    Not in our library10.1073/pnas.0305937101

  23. 23.

    Fauré A Naldi A Lopez F Chaouiya C Ciliberto A Thieffry D Modular logical modelling of the budding yeast cell cycleMol Biosyst2009 7178796

    Not in our library10.1039/b910101m

  24. 24.

    Albert R Othmer HG The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in drosophila melanogasterJ Theor Biol2003 7118

    Not in our library10.1016/s0022-5193(03)00035-3

  25. 25.

    Sánchez L Chaouiya C Thieffry D Segmenting the fly embryo: logical analysis of the role of the segment polarity cross-regulatory moduleInt J Dev Biol2008 7105975

    Not in our library10.1387/ijdb.072439ls

  26. 26.

    González A Chaouiya C Thieffry D Logical modelling of the role of the Hh pathway in the patterning of the Drosophila wing discBioinformatics2008 7i23440

    Not in our library10.1093/bioinformatics/btn266

  27. 27.
  28. 28.

    Mendoza L Thieffry D Alvarez-Buylla ER Genetic control of flower morphogenesis in Arabidopsis thaliana: a logical analysisBioinformatics1999 7593606

    Not in our library10.1093/bioinformatics/15.7.593

  29. 29.

    Helikar T Kochi N Kowal B Dimri M Naramura M Raja SM Band V Band H Rogers JA A comprehensive, multi-scale dynamical model of ErbB receptor signal transduction in human mammary epithelial cellsPLoS One2013 7e61757

    Not in our library10.1371/journal.pone.0061757

  30. 30.
  31. 31.

    Hinkelmann F Brandon M Guang B McNeill R Blekherman G Veliz-Cuba A Laubenbacher R ADAM: analysis of discrete models of biological systems using computer algebraBMC Bioinforma2011 7295

    Not in our library10.1186/1471-2105-12-295

  32. 32.

    Müssel C Hopfensitz M Kestler HA BoolNet–an R package for generation, reconstruction and analysis of Boolean networksBioinformatics2010 7137880

    Not in our library10.1093/bioinformatics/btq124

  33. 33.
  34. 34.

    Helikar T Kowal B Rogers JA A cell simulator platform: the cell collectiveClin Pharmacol Ther2013 73935

    Not in our library10.1038/clpt.2013.41

  35. 35.
  36. 36.
  37. 37.

    Helikar T Rogers JA ChemChains: a platform for simulation and analysis of biochemical networks aimed to laboratory scientistsBMC Syst Biol2009 758

    Not in our library10.1186/1752-0509-3-58

  38. 38.

    Naldi A Berenguier D Fauré A Lopez F Thieffry D Chaouiya C Logical modelling of regulatory networks with GINsim 2.3Biosystems2009 7134139

    Not in our library10.1016/j.biosystems.2009.04.008

  39. 39.

    Krumsiek J Pölsterl S Wittmann DM Theis FJ Odefy–from discrete to continuous modelsBMC Bioinform2010 7233

    Not in our library10.1186/1471-2105-11-233

  40. 40.

    Zheng J Zhang D Przytycki PF Zielinski R Capala J Przytycka TM SimBoolNet–a cytoscape plugin for dynamic simulation of signaling networksBioinformatics2010 71412

    Not in our library10.1093/bioinformatics/btp617

  41. 41.

    Di Cara A Garg A De Micheli G Xenarios I Mendoza L Dynamic simulation of regulatory networks using SQUADBMC Bioinform2007 7462

    Not in our library10.1186/1471-2105-8-462

  42. 42.

    Clarke EM Grumberg O Peled D Model-checking1999 Cambridge, MA: MIT Press330

    Not in our library

  43. 43.

    Batt G Ropers D de Jong H Geiselmann J Mateescu R Page M Schneider D Validation of qualitative models of genetic regulatory networks by model checking: analysis of the nutritional stress response in Escherichia coliBioinformatics2005 7Suppl 1i1928

    Not in our library10.1093/bioinformatics/bti1048

  44. 44.

    Cimatti A Clarke E Giunchiglia E Giunchiglia F Pistore M Roveri M Sebastiani R Tacchella A NuSMV 2: an OpenSource tool for symbolic model checkingLect Notes Comp Sci2002 735964

    Not in our library10.1007/3-540-45657-0_29

  45. 45.

    Bernot G Comet J-P Richard A Guespin J Application of formal methods to biological regulatory networks: extending Thomas’ asynchronous logical approach with temporal logicJ Theor Biol2004 733947

    Not in our library10.1016/j.jtbi.2004.04.003

  46. 46.

    Chabrier-Rivier N Fages F Soliman S The biochemical abstract machine BIOCHAMLect Notes Comp Sci2005 717191

    Not in our library

  47. 47.

    Monteiro PT Chaouiya C Efficient verification for logical models of regulatory networksAdv Intell Soft Comput2012 725967

    Not in our library10.1007/978-3-642-28839-5_30

  48. 48.

    Monteiro PT Ropers D Mateescu R Freitas AT de Jong H Temporal logic patterns for querying dynamic models of cellular interaction networksBioinformatics2008 7i22733

    Not in our library10.1093/bioinformatics/btn275

  49. 49.

    Carrillo M Góngora PA Rosenblueth DA An overview of existing modeling tools making use of model checking in the analysis of biochemical networksFront Plant Sci2012 7155

    Not in our library10.3389/fpls.2012.00155

  50. 50.

    Hucka M Finney A Sauro HM Bolouri H Doyle JC Kitano H Arkin AP Bornstein BJ Bray D Cornish-Bowden A Cuellar AA Dronov S Gilles ED Ginkel M Gor V Goryanin II Hedley WJ Hodgman TC Hofmeyr J-H Hunter PJ Juty NS Kasberger JL Kremling A Kummer U Le Novere N Loew LM Lucio D Mendes P Minch E Mjolsness ED The systems biology markup language (SBML): a medium for representation and exchange of biochemical network modelsBioinformatics2003 7524531

    Not in our library10.1093/bioinformatics/btg015

  51. 51.

    Le Novère N Hucka M Mi H Moodie S Schreiber F Sorokin A Demir E Wegner K Aladjem MI Wimalaratne SM Bergman FT Gauges R Ghazal P Kawaji H Li L Matsuoka Y Villéger A Boyd SE Calzone L Courtot M Dogrusoz U Freeman TC Funahashi A Ghosh S Jouraku A Kim S Kolpakov F Luna A Sahle S Schmidt E The systems biology graphical notationNat Biotechnol2009 773541

    Not in our library10.1038/nbt.1558

  52. 52.

    Hardy S Robillard PN Modeling and simulation of molecular biology systems using petri nets: modeling goals of various approachesJ Bioinform Comput Biol2004 7595613

    Not in our library10.1142/s0219720004000752

  53. 53.

    Chaouiya C Petri net modelling of biological networksBrief Bioinform2007 72109

    Not in our library10.1093/bib/bbm029

  54. 54.

    Koch I Heiner M Junker BH, Schreiber FPetri netsBiol Netw Anal2008 Hoboken, New Jersey: John Wiley & Sons139179

    Not in our library

  55. 55.

    Rohr C Marwan W Heiner M Snoopy–a unifying Petri net framework to investigate biomolecular networksBioinformatics2010 79745

    Not in our library10.1093/bioinformatics/btq050

  56. 56.

    Bornstein BJ Keating SM Jouraku A Hucka M LibSBML: an API library for SBMLBioinformatics2008 78801

    Not in our library10.1093/bioinformatics/btn051

  57. 57.

    Dräger A Rodriguez N Dumousseau M Dörr A Wrzodek C Le Novère N Zell A Hucka M JSBML: a flexible Java library for working with SBMLBioinformatics2011 721678

    Not in our library10.1093/bioinformatics/btr361

  58. 58.

    Saez-Rodriguez J Alexopoulos LG Epperlein J Samaga R Lauffenburger DA Klamt S Sorger PK Discrete logic modelling as a means to link protein signalling networks with functional analysis of mammalian signal transductionMol Syst Biol2009 7331

    Not in our library10.1038/msb.2009.87

  59. 59.
  60. 60.

    Egea JA Henriques D Cokelear T Villaverde AF Banga JR Saez-Rodriguez J MEIGO: a software suite based on metaheuristics for global optimization in systems biology and bioinformaticsSubmitted (available on arXiv.org: http://arxiv.org/abs/1311.5735)

    Not in our library10.1186/1471-2105-15-136

  61. 61.

    Guziolowski C Videla S Eduati F Thiele S Cokelaer T Siegel A Saez-Rodriguez J Exhaustively characterizing feasible logic models of a signaling network using answer Set programmingBioinformatics2013 723206

    Not in our library10.1093/bioinformatics/btt393

  62. 62.

    Saez-Rodriguez J Alexopoulos LG Zhang M Morris MK Lauffenburger DA Sorger PK Comparing signaling networks between normal and transformed hepatocytes using discrete logical modelsCancer Res2011 7540011

    Not in our library10.1158/0008-5472.can-10-4453

  63. 63.

    Eduati F De Las Rivas J Di Camillo B Toffolo G Saez-Rodriguez J Integrating literature-constrained and data-driven inference of signalling networksBioinformatics2012 723112317

    Not in our library10.1093/bioinformatics/bts363

  64. 64.

    Chaouiya C Naldi A Thieffry D Logical modelling of gene regulatory networks with GINsimMethods Mol Biol2012 746379

    Not in our library10.1007/978-1-61779-361-5_23

  65. 65.

    Thieffry D Dynamical roles of biological regulatory circuitsBrief Bioinform2007 72205

    Not in our library10.1093/bib/bbm028

  66. 66.

    Bérenguier D Chaouiya C Monteiro PT Naldi A Remy E Thieffry D Tichit L Dynamical modeling and analysis of large cellular regulatory networksChaos An Interdiscip J Nonlinear Sci2013 7025114

    Not in our library10.1063/1.4809783

  67. 67.

    Naldi A Remy E Thieffry D Chaouiya C Dynamically consistent reduction of logical regulatory graphsTheor Comput Sci2011 721220718

    Not in our library10.1016/j.tcs.2010.10.021

  68. 68.

    Naldi A Monteiro P Chaouiya C Efficient handling of large signalling-regulatory networks by focusing on their core controlLect Notes Comp Sci2012 7288306

    Not in our library

  69. 69.

    Helikar T Kowal B Madrahimov A Shrestha M Pedersen J Limbu K Thapa I Rowley T Satalkar R Kochi N Konvalina J Rogers JA Bio-logic builder: a non-technical tool for building dynamical, qualitative modelsPLoS One2012 7e46417

    Not in our library10.1371/journal.pone.0046417

  70. 70.

    Qualitative models, version 1 release 1http://identifiers.org/combine.specifications/sbml.level-3.version-1.qual.version-1.release-1

    Not in our library

  71. 71.

    MacNamara A Terfve C Henriques D Bernabé BP Saez-Rodriguez J State-time spectrum of signal transduction logic modelsPhys Biol2012 7045003

    Not in our library10.1088/1478-3975/9/4/045003

  72. 72.

    Gonçalves E van Iersel M Saez-Rodriguez J CySBGN: a cytoscape plug-in to integrate SBGN mapsBMC Bioinform2013 717

    Not in our library10.1186/1471-2105-14-17

  73. 73.

    Wrzodek C Büchel F Ruff M Dräger A Zell A Precise generation of systems biology models from KEGG pathwaysBMC Syst Biol2013 715

    Not in our library10.1186/1752-0509-7-15

  74. 74.
  75. 75.

    Batt G Besson B Ciron PE de Jong H Dumas E Geiselmann J Monte R Monteiro PT Page M Rechenmann F Ropers D Genetic network analyzer: a tool for the qualitative modeling and simulation of bacterial regulatory networksMethods Mol Biol2012 743962

    Not in our library10.1007/978-1-61779-361-5_22

  76. 76.

    Chelliah V Laibe C Le Novère N BioModels database: a repository of mathematical models of biological processesMethods Mol Biol2013 718999

    Not in our library10.1007/978-1-62703-450-0_10

  77. 77.

    Glass L Kauffman SA The logical analysis of continuous, non-linear biochemical control networksJ Theor Biol1973 710329

    Not in our library10.1016/0022-5193(73)90208-7

  78. 78.

    Alur R Belta C Ivančić F Kumar V Mintz M Pappas GJ Rubin H Schug J Hybrid modeling and simulation of biomolecular networkHybrid Syst Comput Control2001 Heidelberg: Springer Berlin Heidelberg1932

    Not in our library

  79. 79.

    Brazma A Cerans K Ruklisa D Schlitt T Viksna J HSM - a hybrid system based approach for modelling intracellular networksGene2013 7707

    Not in our library10.1016/j.gene.2012.11.084

  80. 80.

    Mestl T Plahte E Omholt SW A mathematical framework for describing and analysing gene regulatory networksJ Theor Biol1995 7291300

    Not in our library10.1006/jtbi.1995.0199

  81. 81.
  82. 82.

    Batt G Salah RB Maler O Raskin J-F, Thiagarajan PSOn timed models of gene networksForm model anal timed syst: volume 47632007 Berlin, Heidelberg: Springer Berlin Heidelberg3852

    Not in our library

  83. 83.

    Siebert H Bockmayr A Temporal constraints in the logical analysis of regulatory networksTheor Comput Sci2008 7258275

    Not in our library10.1016/j.tcs.2007.11.010

  84. 84.

    Morris MK Shriver Z Sasisekharan R Lauffenburger DA Querying quantitative logic models (Q2LM) to study intracellular signaling networks and cell-cytokine interactionsBiotechnol J2012 737486

    Not in our library10.1002/biot.201100222

  85. 85.

    Waltemath D Adams R Beard DA Bergmann FT Bhalla US Britten R Chelliah V Cooling MT Cooper J Crampin EJ Garny A Hoops S Hucka M Hunter P Klipp E Laibe C Miller AK Moraru I Nickerson D Nielsen P Nikolski M Sahle S Sauro HM Schmidt H Snoep JL Tolle D Wolkenhauer O Le Novère N Minimum information about a simulation experiment (MIASE)PLoS Comput Biol2011 7e1001122

    Not in our library10.1371/journal.pcbi.1001122

  86. 86.

    Courtot M Juty N Knüpfer C Waltemath D Zhukova A Dräger A Dumontier M Finney A Golebiewski M Hastings J Hoops S Keating S Kell DB Kerrien S Lawson J Lister A Lu J Machne R Mendes P Pocock M Rodriguez N Villeger A Wilkinson DJ Wimalaratne S Laibe C Hucka M Le Novère N Controlled vocabularies and semantics in systems biologyMol Syst Biol2011 7543

    Not in our library10.1038/msb.2011.77

  87. 87.

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