Assembly of Logic-Based Diagrams of Biological Pathways
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.
KeywordsPathway modelling Notation scheme Process diagram Graphical representation
- 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:D418–424PubMedCentralPubMedCrossRefGoogle 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:RESEARCH0012Google 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 4:65Google 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:D452–455PubMedCentralPubMedCrossRefGoogle 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 19:524–531PubMedCrossRefGoogle 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 27:735–741PubMedCrossRefGoogle 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:D411–414PubMedCentralPubMedCrossRefGoogle Scholar
- Moodie SL, Sorokin A, Goryanin I, Ghazal P (2006) A graphical notation to describe the logical interactions of biological pathways. J Integr Bioinform 3:11Google 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 27:735–741PubMedCrossRefGoogle 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 0015Google 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 4:63Google 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 31:334–341PubMedCentralPubMedCrossRefGoogle 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 13Google Scholar