Skip to main content
SpringerLink
Log in

A basis for a visual language for describing, archiving and analyzing functional models of complex biological systems

  • Research
  • Published:
Genome Biology Aims and scope Submit manuscript

Abstract

Background

We propose that a computerized, internet-based graphical description language for systems biology will be essential for describing, archiving and analyzing complex problems of biological function in health and disease.

Results

We outline here a conceptual basis for designing such a language and describe BioD, a prototype language that we have used to explore the utility and feasibility of this approach to functional biology. Using example models, we demonstrate that a rather limited lexicon of icons and arrows suffices to describe complex cell-biological systems as discrete models that can be posted and linked on the internet.

Conclusions

Given available computer and internet technology, BioD may be implemented as an extensible, multidisciplinary language that can be used to archive functional systems knowledge and be extended to support both qualitative and quantitative functional analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Karp PD: Metabolic databases. Trends Biochem Sci. 1998, 23: 114-116. 10.1016/S0968-0004(98)01184-0.

    Article  PubMed  CAS  Google Scholar 

  2. From sequence to function. An introduction to the KEGG project. [http://kegg.genome.ad.jp/kegg/kegg2.html]

  3. McAdams HH, Shapiro L: Circuit simulation of genetic networks. Science. 1995, 269: 650-656.

    Article  PubMed  CAS  Google Scholar 

  4. Takai-Igarashi T, Nadaoka Y, Kaminuma T: A database for cell signaling networks. J Comput Biol. 1998, 5: 747-754.

    Article  PubMed  CAS  Google Scholar 

  5. Transpath home page. [http://193.175.244.148/index.html]

  6. Kohn KW: Molecular interaction map of the mammalian cell cycle control and DNA repair systems. Mol Biol Cell. 1999, 10: 2703-2734.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. MODULES in extracellular proteins. [http://www.bork.embl-heidelberg.de/Modules/extra.html]

  8. BioD model of G1/S checkpoint machinery. [http://www.rainbio.com/BioD_G1-S.html]

  9. BioD model of the ketogenic diet and epilepsy. [http://depts.washington.edu/perc/infoscientists/ketogenicdiet/KD_Events.html]

  10. Sherr CJ, Roberts JM: Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995, 9: 1149-1163.

    Article  PubMed  CAS  Google Scholar 

  11. Harper JW, Elledge SJ: Cdk inhibitors in development and cancer. Curr Opin Genet Dev. 1996, 6: 56-64.

    Article  PubMed  CAS  Google Scholar 

  12. Sherr CJ: Cancer cell cycles. Science. 1996, 274: 1672-1677. 10.1126/science.274.5293.1672.

    Article  PubMed  CAS  Google Scholar 

  13. Kaldis P: The cdk-activating kinase (CAK): from yeast to mammals. Cell Mol Life Sci. 1999, 55: 284-296. 10.1007/s000180050290.

    Article  PubMed  CAS  Google Scholar 

  14. Sherr CJ, Roberts JM: CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999, 13: 1501-1512.

    Article  PubMed  CAS  Google Scholar 

  15. Ptashne M: A Genetic Switch. Cambridge, MA: Cell Press;. 1992, 20-28.

    Google Scholar 

  16. Gelbart WM: Databases in genomic research. Science. 1998, 282: 659-661. 10.1126/science.282.5389.659.

    Article  PubMed  CAS  Google Scholar 

  17. Extensible Markup Language (XML) 1.0 (Second Edition). [http://www.w3.org/TR/REC-xml]

  18. Mackenzie D: New language could meld the Web into a seamless database. Science. 1998, 280: 1840-1841. 10.1126/science.280.5371.1840.

    Article  CAS  Google Scholar 

  19. Fenyo D: The Biopolymer Markup Language. Bioinformatics. 1999, 15: 339-340. 10.1093/bioinformatics/15.4.339.

    Article  PubMed  CAS  Google Scholar 

  20. The Physiome Markup Languages. [http://www.physiome.org.nz/]

  21. Systems Biology Markup Language [SBML]. [http://www.cds.caltech.edu/erato/index.html]

  22. XML Linking Language (XLink) Version 1.0. [http://www.w3.org/TR/xlink/]

  23. McHugh J, Abiteboul S, Goldman R, Quass D, Widom J: Lore: A database management system for semistructured data. SIGMOD Record. 1997, 26: 54-66.

    Article  Google Scholar 

  24. Backlund B, Hagsand O, Pehrson B: Generation of visual language-oriented design environments. J Vis Lang Comput. 1990, 1: 333-354.

    Article  Google Scholar 

  25. Meyers BA: Taxonomies of visual programming and program visualization. J Vis Lang Comput. 1990, 1: 97-123.

    Article  Google Scholar 

  26. Hargrove JL, Hulsey MG, Summers AO: From genotype to phenotype: computer-based modeling of gene expression with STELLA II. Biotechniques. 1993, 15: 1096-1101.

    PubMed  CAS  Google Scholar 

  27. Barrett PH, Bell BM, Cobelli C, Golde H, Schumitzky A, Vicini P, Foster DM: SAAM II: Simulation, Analysis, and Modeling Software for tracer and pharmacokinetic studies. Metabolism. 1998, 47: 484-492.

    Article  PubMed  CAS  Google Scholar 

  28. Cobelli C, Foster DM: Compartmental models: theory and practice using the SAAM II software system. Adv Exp Med Biol. 1998, 445: 79-101.

    Article  PubMed  CAS  Google Scholar 

  29. Cook DL, Atkins WM: Enhanced detoxification due to distributive catalysis and toxic thresholds: A kinetic analysis. Biochemistry. 1997, 36: 10801-10806. 10.1021/bi971284b.

    Article  PubMed  CAS  Google Scholar 

  30. Cook DL, Gerber AN, Tapscott SJ: Modeling stochastic gene expression: implications for haploinsufficiency. Proc Natl Acad Sci USA. 1998, 95: 15641-15646. 10.1073/pnas.95.26.15641.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Bonarini A, Maniezzo V: Integrating qualitative and quantitative modeling. Int J Expert Systems Res Appl. 1991, 4: 51-70.

    Google Scholar 

  32. Fishwick PA, Zeigler BP: Creating Qualitative and Combined Models with Discrete Events. IEEE/Computer Society Press: Los Alamitos, CA,. 1991

    Google Scholar 

  33. Kuipers BJ: Reasoning with qualitative models. Artificial Intelligence. 1993, 59: 1-2. 10.1016/0004-3702(93)90162-5.

    Article  Google Scholar 

  34. Kuipers BJ, Shults B: Reasoning in Logic About Continuous Systems. San Francisco, CA: Morgan Kaufman Publ.;. 1994

    Google Scholar 

  35. Eisenberg M: The kineticist's workbench: qualitative/quantitative simulation of chemical reaction mechanisms. Expert Systems Appl. 1991, 3: 367-377. 10.1016/0957-4174(91)90059-N.

    Article  Google Scholar 

  36. Ursino M, Avanzolini G, Barbini P: Qualitative simulation of dynamic physiological models using the KEE environment. Artificial Intelligence Med. 1992, 4: 53-73.

    Article  Google Scholar 

  37. Tyson JJ, Novak B, Odell GM, Chen K, Thron CD: Chemical kinetic theory: understanding cell-cycle regulation. Trends Biochem Sci. 1996, 21: 89-96. 10.1016/0968-0004(96)10011-6.

    Article  PubMed  CAS  Google Scholar 

  38. Thieffry D, Thomas R: Qualitative analysis of gene networks. Pac Symp Biocomput. 1998, 77-88.

    Google Scholar 

  39. KineCyte™ biological systems simulator. [http://www.rainbio.com/KineCyte.html]

  40. Glasgow J, Narayanan NH, Chandrasekaran B: Diagrammatic Reasoning: Cognitive and Computational Perspectives. Cambridge, MA, The AAAI Press;. 1995

    Google Scholar 

  41. Corkill DD: Blackboard systems. AI Expert. 1991, 6: 40-47.

    Google Scholar 

  42. Buschmann F, Meunier R, Rohnert H, Sommerlad P, Stal M: Pattern-Oriented Software Architecture; A System of Patterns. New York: John Wiley and Sons;. 1996

    Google Scholar 

  43. DiBona C, Ockman S, Stone M: Open Sources: Voices from the Open Source Revolution. Sebastopol, CA: O'Reilly & Associates, Inc; 1999).

  44. Gille H, Downward J: Multiple ras effector pathways contribute to G(1) cell cycle progression. J Biol Chem. 1999, 274: 22033-22040. 10.1074/jbc.274.31.22033.

    Article  PubMed  CAS  Google Scholar 

  45. Diehl JA, Cheng M, Roussel MF, Sherr CJ: Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 1998, 12: 3499-3511.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  46. Woodfork KA, Wonderlin WF, Peterson VA, Strobl JS: Inhibition of ATP-sensitive potassium channels causes reversible cell-cycle arrest of human breast cancer cells in tissue culture. J Cell Physiol. 1995, 162: 163-171.

    Article  PubMed  CAS  Google Scholar 

  47. Heist EK, Schulman H: The role of Ca2+/calmodulin-dependent protein kinases within the nucleus. Cell Calcium. 1998, 23: 103-114.

    Article  PubMed  CAS  Google Scholar 

  48. Wang S, Melkoumian Z, Woodfork KA, Cather C, Davidson AG, Wonderlin WF, Strobl JS: Evidence for an early G1 ionic event necessary for cell cycle progression and survival in the MCF-7 human breast carcinoma cell line. J Cell Physiol. 1998, 176: 456-464. 10.1002/(SICI)1097-4652(199809)176:3<456::AID-JCP2>3.3.CO;2-Z.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Jim Roberts, Dan Gottschling and Barbara Trask for helpful discussion during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA

    Daniel L Cook & Stephen J Tapscott

  2. RainTown, 331 N 72nd St, Seattle, WA, 98103, USA

    Daniel L Cook & Joel F Farley

Authors
  1. Daniel L Cook
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joel F Farley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephen J Tapscott
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel L Cook.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cook, D.L., Farley, J.F. & Tapscott, S.J. A basis for a visual language for describing, archiving and analyzing functional models of complex biological systems. Genome Biol 2, research0012.1 (2001). https://doi.org/10.1186/gb-2001-2-4-research0012

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/gb-2001-2-4-research0012

Keywords

Search

Navigation