Skip to main content
SpringerLink
Log in

Assembly of Logic-Based Diagrams of Biological Pathways

  • Chapter
  • First Online:
Systems Biology for Signaling Networks

Part of the book series: Systems Biology ((SYSTBIOL))

  • 1970 Accesses

Abstract

The networks of molecular interactions that underpin cellular function are highly complex and dynamic. The topology, behaviour and logic of these systems, even on a relatively small scale, are far too complicated to understand intuitively. Furthermore, enormous amounts of systems-level data pertaining to the nature of genes and proteins, and their potential cellular interactions, have now been generated, but we struggle to interpret these data. There is therefore general agreement amongst biologists about the need for good pathway diagrams. However, the challenge of creating models that reflect our current understanding of these systems and displaying this information in an intuitive and logical manner is not trivial. The modified Edinburgh pathway notation (mEPN) scheme is founded on a notation system originally devised a number of years ago, but through use has now been refined extensively. This has been primarily driven by the author’s attempts to produce process diagrams for a diverse range of biological pathways, particularly with respect to immune signalling in mammals. Whilst requiring a considerable effort, the assembly of pathway models provides a resource for training, literature/data interpretation, computational pathway modelling and hypothesis generation. Here I discuss the mEPN scheme, its symbols and rules for its use and thereby hope to provide a coherent guide to those planning to construct pathway diagrams of their biological systems of interest.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alfarano C, Andrade CE, Anthony K, Bahroos N, Bajec M, Bantoft K, Betel D, Bobechko B, Boutilier K, Burgess E, Buzadzija K, Cavero R, D'Abreo C, Donaldson I, Dorairajoo D, Dumontier MJ, Dumontier MR, Earles V, Farrall R, Feldman H et al (2005) The biomolecular interaction network database and related tools 2005 update. Nucleic Acids Res 33:D418–424

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Antonov AV, Dietmann S, Mewes HW (2008) KEGG spider: interpretation of genomics data in the context of the global gene metabolic network. Genome Biol 9:R179

    Article  PubMed Central  PubMed  Google Scholar 

  • Arakawa K, Kono N, Yamada Y, Mori H, Tomita M (2005) KEGG-based pathway visualization tool for complex omics data. In Silico Biol 5:419–423

    CAS  PubMed  Google Scholar 

  • Babur O, Colak R, Demir E, Dogrusoz U (2008) PATIKAmad: putting microarray data into pathway context. Proteomics 8:2196–2198

    Article  CAS  PubMed  Google Scholar 

  • Bader GD, Cary MP, Sander C (2006) Pathguide: a pathway resource list. Nucleic Acids Res 34:D504–506

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Calzone L, Gelay A, Zinovyev A, Radvanyi F, Barillot E (2008) A comprehensive modular map of molecular interactions in RB/E2F pathway. Mol Syst Biol 4:173

    Article  PubMed Central  PubMed  Google Scholar 

  • Cassman M (2005) Barriers to progress in systems biology. Nature 438:1079

    Article  CAS  PubMed  Google Scholar 

  • Cavalieri D, De Filippo C (2005) Bioinformatic methods for integrating whole-genome expression results into cellular networks. Drug Discov Today 10:727–734

    Article  CAS  PubMed  Google Scholar 

  • Cook DL, Farley JF, Tapscott SJ (2001) A basis for a visual language for describing, archiving and analyzing functional models of complex biological systems. Genome Biol 2:RESEARCH0012

    Google Scholar 

  • Dahlquist KD, Salomonis N, Vranizan K, Lawlor SC, Conklin BR (2002) GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways. Nat Genet 31:19–20

    Article  CAS  PubMed  Google Scholar 

  • Ekins S, Nikolsky Y, Bugrim A, Kirillov E, Nikolskaya T (2007) Pathway mapping tools for analysis of high content data. Methods Mol Biol 356:319–350

    CAS  PubMed  Google Scholar 

  • Eungdamrong NJ, Iyengar R (2004) Modeling cell signaling networks. Biol Cell 96:355–362

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Freeman TC, Goldovsky L, Brosch M, van Dongen S, Maziere P, Grocock RJ, Freilich S, Thornton J, Enright AJ (2007) Construction, visualisation, and clustering of transcription networks from microarray expression data. PLoS Comput Biol 3:2032–2042

    Article  CAS  PubMed  Google Scholar 

  • Freeman TC, Raza S, Theocharidis A, Ghazal P (2010) The mEPN Scheme: an intuitive and flexible graphical system for rendering biological pathways BMC Syst Biol 4:65

    Google Scholar 

  • Funahashi A, Matsuoka Y, Jouraku A, Morohashi M, Kikuchi N, Kitano H (2008) CellDesigner 3.5: A versatile modeling tool for biochemical networks. Proc IEEE 96:1254–1265

    Article  Google Scholar 

  • Hermjakob H, Montecchi-Palazzi L, Lewington C, Mudali S, Kerrien S, Orchard S, Vingron M, Roechert B, Roepstorff P, Valencia A, Margalit H, Armstrong J, Bairoch A, Cesareni G, Sherman D, Apweiler R (2004) IntAct: an open source molecular interaction database. Nucleic Acids Res 32:D452–455

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Accessed on June 1, 2010. http://www.biopax.org/. Biological Pathways Exchange

  • Accessed on June 1, 2010. http://www.ingenuity.com/. Ingenuity Pathway Analysis.

  • Accessed on June 1, 2010. http://www.yworks.com. yEd Graph Editor – yWorks the diagramming company.

  • 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 JH, Hunter PJ et al (2003) The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19:524–531

    Article  CAS  PubMed  Google Scholar 

  • Janssen P, Audit B, Cases I, Darzentas N, Goldovsky L, Kunin V, Lopez-Bigas N, Peregrin-Alvarez JM, Pereira-Leal JB, Tsoka S, Ouzounis CA (2003) Beyond 100 genomes. Genome Biol 4:402

    Article  PubMed Central  PubMed  Google Scholar 

  • Jensen LJ, Kuhn M, Stark M, Chaffron S, Creevey C, Muller J, Doerks T, Julien P, Roth A, Simonovic M, Bork P, von Mering C (2009) STRING 8–a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res 37:D412–416

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Joshi-Tope G, Gillespie M, Vastrik I, D’Eustachio P, Schmidt E, de Bono B, Jassal B, Gopinath GR, Wu GR, Matthews L, Lewis S, Birney E, Stein L (2005) Reactome: a knowledgebase of biological pathways. Nucleic Acids Res 33:D428–432

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27–30

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kitano H (2002) Computational systems biology. Nature 420:206–210

    Article  CAS  PubMed  Google Scholar 

  • Kitano H, Funahashi A, Matsuoka Y, Oda K (2005) Using process diagrams for the graphical representation of biological networks. Nat Biotechnol 23:961–966

    Article  CAS  PubMed  Google Scholar 

  • Kohn KW (1999) Molecular interaction map of the mammalian cell cycle control and DNA repair systems. Mol Biol Cell 10:2703–2734

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kwiatkowska MZ, Heath JK (2009) Biological pathways as communicating computer systems. J Cell Sci 122:2793–2800

    Article  CAS  PubMed  Google Scholar 

  • Le Novère N, Hucka M, Mi H, Moodie S, Shreiber 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, Watterson S, Wu G, Goryanin I, Kell DB, Sander C, Sauro H, Snoep JL, Kohn K, Kitano H. (2009) The systems biology graphical notation. Nat Biotechnol 27:735–741

    Article  PubMed  Google Scholar 

  • Lloyd CM, Halstead MD, Nielsen PF (2004) CellML: its future, present and past. Prog Biophys Mol Biol 85:433–450

    Article  CAS  PubMed  Google Scholar 

  • Luciano JS (2005) PAX of mind for pathway researchers. Drug Discov Today 10:937–942

    Article  CAS  PubMed  Google Scholar 

  • Mishra GR, Suresh M, Kumaran K, Kannabiran N, Suresh S, Bala P, Shivakumar K, Anuradha N, Reddy R, Raghavan TM, Menon S, Hanumanthu G, Gupta M, Upendran S, Gupta S, Mahesh M, Jacob B, Mathew P, Chatterjee P, Arun KS et al (2006) Human protein reference database—2006 update. Nucleic Acids Res 34:D411–414

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Moodie SL, Sorokin A, Goryanin I, Ghazal P (2006) A graphical notation to describe the logical interactions of biological pathways. J Integr Bioinform 3:11

    Google Scholar 

  • Novere NL, 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, Villeger A, Boyd SE, Calzone L, Courtot M et al (2009) The systems biology graphical notation. Nat Biotechnol 27:735–741

    Article  PubMed  Google Scholar 

  • Nurse P (2003) Systems biology: understanding cells. Nature 424:883

    Article  CAS  PubMed  Google Scholar 

  • Oda K, Kimura T, Matsuoka Y, Funahashi A, M. M, Kitano H. (2004) Molecular interaction map of a macrophage. The alliance for cellular signaling (AfCS) Research Reports, vol. 2, http://www.signaling-gateway.org/reports/v2/DA0014/DA0014.htm

  • Oda K, Kitano H (2006) A comprehensive map of the toll-like receptor signaling network. Mol Syst Biol 2:2006 0015

    Google Scholar 

  • Pandey R, Guru RK, Mount DW (2004) Pathway Miner: extracting gene association networks from molecular pathways for predicting the biological significance of gene expression microarray data. Bioinformatics 20:2156–2158

    Article  CAS  PubMed  Google Scholar 

  • Pavlopoulos GA, Wegener, A-L., Schneider, R. (2008) A survey of visualization tools for biological network analysis. BioData Mining 1:12

    Article  PubMed Central  PubMed  Google Scholar 

  • Pico AR, Kelder T, van Iersel MP, Hanspers K, Conklin BR, Evelo C (2008) WikiPathways: pathway editing for the people. PLoS Biol 6:e184

    Article  PubMed Central  PubMed  Google Scholar 

  • Pirson I, Fortemaison N, Jacobs C, Dremier S, Dumont JE, Maenhaut C (2000) The visual display of regulatory information and networks. Trends Cell Biol 10:404–408

    Article  CAS  PubMed  Google Scholar 

  • Raza S, McDerment N, Lacaze PA, Robertson K, Watterson S, Chen Y, Chisholm M, Eleftheriadis G, Monk S, O’Sullivan M, Turnbull A, Roy D, Theocharidis A, Ghazal P, Freeman TC (2010) Construction of a large scale integrated map of macrophage pathogen recognition and effector systems. BMC Syst Biol 4:63

    Google Scholar 

  • Raza S, Robertson KA, Lacaze PA, Page D, Enright AJ, Ghazal P, Freeman TC (2008) A logic-based diagram of signalling pathways central to macrophage activation. BMC Syst Biol 2:36

    Article  PubMed Central  PubMed  Google Scholar 

  • Reed JL, Famili I, Thiele I, Palsson BO (2006) Towards multidimensional genome annotation. Nat Rev Genet 7:130–141

    Article  CAS  PubMed  Google Scholar 

  • Ruths D, Muller M, Tseng JT, Nakhleh L, Ram PT (2008) The signaling petri net-based simulator: a non-parametric strategy for characterizing the dynamics of cell-specific signaling networks. PLoS Comput Biol 4:e1000005

    Article  PubMed Central  PubMed  Google Scholar 

  • Schaefer CF, Anthony K, Krupa S, Buchoff J, Day M, Hannay T, Buetow KH (2009) PID: the Pathway Interaction Database. Nucleic Acids Res 37:D674–679

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Thomas PD, Kejariwal A, Campbell MJ, Mi H, Diemer K, Guo N, Ladunga I, Ulitsky-Lazareva B, Muruganujan A, Rabkin S, Vandergriff JA, Doremieux O (2003) PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification. Nucleic Acids Res 31:334–341

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • van Riel NA (2006) Dynamic modelling and analysis of biochemical networks: mechanism-based models and model-based experiments. Brief Bioinform 7:364–374

    Article  PubMed  Google Scholar 

  • Vastrik I, D’Eustachio P, Schmidt E, Gopinath G, Croft D, de Bono B, Gillespie M, Jassal B, Lewis S, Matthews L, Wu G, Birney E, Stein L (2007) Reactome: a knowledge base of biologic pathways and processes. Genome Biol 8:R39

    Article  PubMed Central  PubMed  Google Scholar 

  • Watterson S, Marshall S, Ghazal P (2008) Logic models of pathway biology. Drug Discov Today 13:447–456

    Article  CAS  PubMed  Google Scholar 

  • Yeung N, Cline MS, Kuchinsky A, Smoot ME, Bader GD (2008) Exploring biological networks with Cytoscape software. Curr Protoc Bioinformatics Chapter 8:Unit 8 13

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, EH25 9PS, UK

    Tom C. Freeman

Authors
  1. Tom C. Freeman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tom C. Freeman .

Editor information

Editors and Affiliations

  1. College of Natural Science, Dept. Biological Science, Department of Molecular Science and Tech, Suwon, 442-749, Korea, Republic of (South Korea)

    Sangdun Choi

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Freeman, T.C. (2010). Assembly of Logic-Based Diagrams of Biological Pathways. In: Choi, S. (eds) Systems Biology for Signaling Networks. Systems Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5797-9_6

Download citation

Publish with us

Policies and ethics

Search

Navigation