The provided guidelines are based on our collective experience of building representations of disease mechanisms, the work by Maria Kondratova and coauthors (Kondratova et al., 2018, PMID 29688383), descriptions of published disease maps (Mizuno et al., 2012, PMID 22647208; Matsuoka et al., 2013, PMID 24088197; Fujita et al., 2014, PMID 23832570; Kuperstein et al., 2015, PMID 26192618; Singh et al., 2018, PMID 29951575) and comprehensive pathway maps (Oda et al., 2005, PMID 16729045; Oda and Kitano, 2006, PMID 16738560; Caron et al., 2010, PMID 21179025).

In each case, a resource is designed while taking into account the goals and objectives of a particular project, specifics of disease conditions and disease subtypes.

Suggested steps

The following order of tasks is shown to be efficient in published and ongoing projects.

  1. Pre-development stage: an initial scan of the relevant literature by searching PubMed.

  2. Forming a panel of domain experts: leading researchers (clinicians and biologist) knowledgeable in the field of the disease.

  3. Determining the scope of the disease map: identifying disease hallmarks, key modules to include and the desired granularity that suits the project.

  4. Designing the architecture of the map.

  5. Developing an overview map and start determining the content in close communication with the domain experts. An overview map outlines the main modules that are to be included and essentially reviews the future content of the detailed representation of disease mechanisms.

  6. Developing the first version of the map reusing information from other disease maps and pathway databases as much as possible to speed up the process of map construction.

  7. Finalising the comprehensive version of the map. The refined version is complete and made accessible online for browsing, data interpretation and hypothesis generation, new disease-specific pathway modules are developed from scratch where necessary.

  8. Making the map accessible via publishing it in one of the online map navigation platforms.

  9. Collecting feedback and regularly updating the map.


We aim at making maps available in various formats including SBGN (Systems Biology Graphical Notation), SBML (Systems Biology Markup Language) and BioPAX (Biological Pathway Exchange), and also in the original format of the tool in which the map was developed, for example, the default CellDesigner’s XML format or the yEd Graph Editor’s GraphML format.

  1. Caron E, Ghosh S, Matsuoka Y, Ashton-Beaucage D, Therrien M, Lemieux S, Perreault C, Roux PP, Kitano H. A comprehensive map of the mTOR signaling network. Mol Syst Biol. 2010 Dec 21;6:453. doi: 10.1038/msb.2010.108. Review. PubMed PMID: 21179025.

  2. Fujita KA, Ostaszewski M, Matsuoka Y, Ghosh S, Glaab E, Trefois C, Crespo I, Perumal TM, Jurkowski W, Antony PM, Diederich N, Buttini M, Kodama A, Satagopam VP, Eifes S, Del Sol A, Schneider R, Kitano H, Balling R. Integrating pathways of Parkinson’s disease in a molecular interaction map. Mol Neurobiol. 2014 Feb;49(1):88-102. doi: 10.1007/s12035-013-8489-4. Epub 2013 Jul 7. Review. PubMed PMID: 23832570.

  3. Kondratova M, Sompairac N, Barillot E, Zinovyev A, Kuperstein I. Signalling maps in cancer research: construction and data analysis. Database (Oxford). 2018 Jan 1;2018. doi: 10.1093/database/bay036. PubMed PMID: 29688383.

  4. Kuperstein I, Bonnet E, Nguyen HA, Cohen D, Viara E, Grieco L, Fourquet S, Calzone L, Russo C, Kondratova M, Dutreix M, Barillot E, Zinovyev A. Atlas of Cancer Signalling Network: a systems biology resource for integrative analysis of cancer data with Google Maps. Oncogenesis. 2015 Jul 20;4:e160. doi: 10.1038/oncsis.2015.19. PubMed PMID: 26192618.

  5. Kuperstein I, Grieco L, Cohen DP, Thieffry D, Zinovyev A, Barillot E. The shortest path is not the one you know: application of biological network resources in precision oncology research. Mutagenesis. 2015 Mar;30(2):191-204. doi: 10.1093/mutage/geu078. Review. PubMed PMID: 25688112.

  6. Matsuoka Y, Matsumae H, Katoh M, Eisfeld AJ, Neumann G, Hase T, Ghosh S, Shoemaker JE, Lopes TJ, Watanabe T, Watanabe S, Fukuyama S, Kitano H, Kawaoka Y. A comprehensive map of the influenza A virus replication cycle. BMC Syst Biol. 2013 Oct 2;7:97. doi: 10.1186/1752-0509-7-97. PubMed PMID: 24088197.

  7. Mizuno S, Iijima R, Ogishima S, Kikuchi M, Matsuoka Y, Ghosh S, Miyamoto T, Miyashita A, Kuwano R, Tanaka H. AlzPathway: a comprehensive map of signaling pathways of Alzheimer’s disease. BMC Syst Biol. 2012 May 30;6:52. doi: 10.1186/1752-0509-6-52. PubMed PMID: 22647208.

  8. Oda K, Kitano H. A comprehensive map of the toll-like receptor signaling network. Mol Syst Biol. 2006;2:2006.0015. Epub 2006 Apr 18. Review. PubMed PMID: 16738560.

  9. Oda K, Matsuoka Y, Funahashi A, Kitano H. A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol. 2005;1:2005.0010. Epub 2005 May 25. PubMed PMID: 16729045.

  10. Singh V, Ostaszewski M, Kalliolias GD, Chiocchia G, Olaso R, Petit-Teixeira E, Helikar T, Niarakis A. Computational Systems Biology Approach for the Study of Rheumatoid Arthritis: From a Molecular Map to a Dynamical Model. Genom Comput Biol. 2018;4(1). pii: e100050. doi: 10.18547/gcb.2018.vol4.iss1.e100050. Epub 2017 Dec 6. PubMed PMID: 29951575.

  11. Thiele I, Palsson BØ. A protocol for generating a high-quality genome-scale metabolic reconstruction. Nat Protoc. 2010 Jan;5(1):93-121. doi: 10.1038/nprot.2009.203. Epub 2010 Jan 7. PubMed PMID: 20057383.