The understanding of complex biological networks often relies on both a dedicated layout and a topology. Currently, there are three major competing layout-aware systems biology formats, but there are no software tools or software libraries supporting all of them. This complicates the management of molecular network layouts and hinders their reuse and extension. In this paper, we present a high-level overview of the layout formats in systems biology, focusing on their commonalities and differences, review their support in existing software tools, libraries and repositories and finally introduce a new conversion module within the MINERVA platform. The module is available via a REST API and offers, besides the ability to convert between layout-aware systems biology formats, the possibility to export layouts into several graphical formats. The module enables conversion of very large networks with thousands of elements, such as disease maps or metabolic reconstructions, rendering it widely applicable in systems biology.

Department of Mathematics Technische Universität München München Germany

Faculty of Mathematics and Natural Sciences University of Bonn Bonn Germany

Faculty of Mathematics and Physics Charles University Malostranské nám 25 118 00 Prague Czech Republic

Institute of Computational Biology Helmholtz Zentrum München German Research Center for Environmental Health Ingolstädter Landstr 1 85764 Neuherberg Germany

Luxembourg Centre for Systems Biomedicine University of Luxembourg 6 avenue du Swing L 4367 Belvaux Luxembourg

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Brief Bioinform. 2021 Jan 18;22(1):608. doi: 10.1093/bib/bbaa030. PubMed

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Kitano H. Systems biology: a brief overview. Science 2002;295:1662–4. PubMed

Mazein A, Ostaszewski M, Kuperstein I, et al. . Systems medicine disease maps: community-driven comprehensive representation of disease mechanisms. NPJ Syst Biol Appl 2018;4:21. PubMed PMC

Noronha A, Daníelsdóttir AD, Gawron P, et al. . ReconMap: an interactive visualization of human metabolism. Bioinformatics 2017;33:605–7. PubMed PMC

Ostaszewski M, Gebel S, Kuperstein I, et al. . Community-driven roadmap for integrated disease maps. Brief Bioinform 2018;1–12. https://academic.oup.com/bib/advance-article/doi/10.1093/bib/bby024/4982567?searchresult=1. PubMed DOI PMC

Siebenhaller M, Nielsen SS, McGee F, et al. . Human-like layout algorithms for signalling hypergraphs: outlining requirements. Brief Bioinform 2018. https://academic.oup.com/bib/advance-article/doi/10.1093/bib/bby099/5115270. PubMed DOI

Hucka M, Finney A, Sauro HM, et al. . The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 2003;19(4):524–31. PubMed

Demir E, Cary MP, Paley S, et al. . The BioPAX community standard for pathway data sharing. Nat Biotechnol 2010;28(9):935. PubMed PMC

Fabregat A, Jupe S, Matthews L, et al. . The Reactome Pathway Knowledgebase. Nucleic Acids Res 2018;42(D1):D472–7. PubMed PMC

Cerami EG, Gross BE, Demir E, et al. . Pathway Commons, a web resource for biological pathway data. Nucleic Acids Res 2011;39(Supp 1):D685–90. PubMed PMC

Hucka M, Bergmann F, Hoops S, et al. . The systems biology markup language (SBML): language specification for level 3 version 1 core (release 1 candidate). Nat Preced 2010. http://precedings.nature.com/documents/4123/version/1. PubMed PMC

Gauges R, Rost U, Sahle S, et al. . The systems biology markup language (SBML) level 3 package: layout, version 1 core. J Integr Bioinform 2015;12(2):550–602. PubMed

Bergmann FT, Keating SM, Gauges R, et al. . SBML level 3 package: render, version 1, release 1. J Integr Bioinform 2018;15(1) https://www.degruyter.com/view/j/jib.2018.15.issue-1/jib-2017-0078/jib-2017-0078.xml PubMed PMC

Le NN, Hucka M, Mi H, et al. . The Systems Biology Graphical Notation. Nat Biotechnol 2009;27(8):735–42. PubMed

Van Iersel MP, Villéger AC, Czauderna T, et al. . Software support for SBGN maps: SBGN-ML and LibSBGN. Bioinformatics 2012;28(15):2016–21. PubMed PMC

Funahashi A, Morohashi M, Kitano H, et al. . CellDesigner: a process diagram editor for gene-regulatory and biochemical networks. Biosilico 2003;1(5):159–62.

Gawron P, Ostaszewski M, Satagopam V, et al. . MINERVA—a platform for visualization and curation of molecular interaction networks. NPJ Syst Biol Appl 2016;2(1):1–6. PubMed PMC

Courtot M, Juty N, Knüpfer C, et al. . Controlled vocabularies and semantics in systems biology. Mol Syst Biol 2011;7(1):543. PubMed PMC

Purchase HC. Metrics for graph drawing aesthetics. J Vis Lang Comput 2002;13(5):501–16.

Zhang F, Meier-Schellersheim M. Multistate, Multicomponent and Multicompartment Species Package for SBML Level 3. http://identifiers.org/combine.specifications/sbml.level-3.version-1.multi.version-1.release-1 (31 May 2019, date last accessed). PubMed PMC

König M. SBGN ML_Extensions. https://github.com/sbgn/sbgn/wiki/SBGN-ML_Extensions/d4ac2c9606bf4f81c2b26edd874d434de23bd153 (31 May 2019, date last accessed).

Kanehisa M, Furumichi M, Tanabe M, et al. . KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 2017;45(D1):D353–61. PubMed PMC

van Iersel MP, Kelder T, Pico AR, et al. . Presenting and exploring biological pathways with PathVisio. BMC Bioinformatics 2008;9(1):399. PubMed PMC

Kutmon M, Riutta A, Nunes N, et al. . WikiPathways: capturing the full diversity of pathway knowledge. Nucleic Acids Res 2016;44(D1):D488–94. PubMed PMC

Ebrahim A, Lerman JA, Palsson BO, et al. . COBRApy: COnstraints-Based Reconstruction and Analysis for Python. BMC Syst Biol 2013;7(1):74. PubMed PMC

Olivier BG, Rohwer JM, Hofmeyr JHS. Modelling cellular systems with PySCeS. Bioinformatics 2005;21(4):560–1. PubMed

Hoops S, Gauges R, Lee C, et al. . COPASI—a COmplex PAthway SImulator. Bioinformatics 2006;22(24):3067–74. PubMed

Darzi Y, Letunic I, Bork P, et al. . IPath3.0: interactive pathways explorer v3. Nucleic Acids Res 2018;46(W1):W510–3. PubMed PMC

Fujita KA, Ostaszewski M, Matsuoka Y, et al. . Integrating pathways of Parkinson’s disease in a molecular interaction map. Mol Neurobiol 2014;49:88–102. PubMed PMC

Olivier BG, Snoep JL. Web-based kinetic modelling using JWS Online. Bioinformatics 2004;20(13):2143–4. PubMed

Shannon P, Markiel A, Ozier O, et al. . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003;13:2498–504. PubMed PMC

König M, Dräger A, Holzhütter HG. CySBML: a cytoscape plugin for SBML. Bioinformatics 2012;28(18):2402–3. PubMed

Gonçalves E, Iersel MV, Saez-Rodriguez J. CySBGN: a cytoscape plug-in to integrate SBGN maps. BMC Bioinformatics 2013;14(1):17. PubMed PMC

i-Vis Information Visualization Lab. Newt Pathway Viewer and Editor. http://web.newteditor.org/ (31 October 2018, date last accessed).

Wiese R. Krayon for SBGN. https://github.com/wiese42/krayon4sbgn (16 April 2019, date last accessed).

Rohn H, Junker A, Hartmann A, et al. . VANTED v2: a framework for systems biology applications. BMC Syst Biol 2012;6(1):139. PubMed PMC

Czauderna T, Klukas C, Schreiber F, et al. . Editing, validating and translating of SBGN maps. Bioinformatics 2011;27:2340–1. PubMed PMC

yWorks. yED Graph Editor. https://www.yworks.com/products/yed (31 October 2018, date last accessed).

SBGN community. ySBGN. https://github.com/sbgn/ySBGN (31 October 2018, date last accessed).

Kuperstein I, Cohen DPA, Pook S, et al. . NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps. BMC Syst Biol 2013;7(1):100. PubMed PMC

Kolpakov F, Puzanov M, Koshukov A.. BioUML: visual modeling, automated code generation and simulation of biological systems. In: Proceedings of the Fifth International Conference on Bioinformatics of Genome Regulation and Structure. Russia: Siberian Branch of the Russian Academy of Sciences, 2006.

King ZA, Lu J, Dräger A, et al. . BiGG models: a platform for integrating, standardizing and sharing genome-scale models. Nucleic Acids Res 2016;44(D1):D515–22. PubMed PMC

Schellenberger J, Que R, Fleming RMT, et al. . Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0. Nat Protoc 2011;6(9):1290. PubMed PMC

King ZA, Dräger A, Ebrahim A, et al. . Escher: a web application for building, sharing, and embedding data-rich visualizations of biological pathways. PLoS Comput Biol 2015;11(8):e1004321. PubMed PMC

Bornstein BJ, Keating SM, Jouraku A, et al. . LibSBML: an API library for SBML. Bioinformatics 2008;24(6):880–1. PubMed PMC

Rodriguez N, Thomas A, Watanabe L, et al. . JSBML 1.0: providing a smorgasbord of options to encode systems biology models. Bioinformatics 2015;31(20):3383–6. PubMed PMC

Roy L. cd2sbgnml. https://github.com/royludo/cd2sbgnml (29 October 2018, date last accessed).

SBML team. JSBML CellDesigner plugin. https://github.com/sbmlteam/jsbml/tree/master/modules/celldesigner/ (4 March 2019, date last accessed).

Funahashi A. CellDesigner parser. https://github.com/funasoul/celldesigner-parser (3 April 2019, date last accessed).

Wrzodek C, Dräger A, Zell A. KEGGtranslator: visualizing and converting the KEGG PATHWAY database to various formats. Bioinformatics 2011;27(16):2314–5. PubMed PMC

Czauderna T, Wybrow M, Marriott K, et al. . Conversion of KEGG metabolic pathways to SBGN maps including automatic layout. BMC Bioinformatics 2013;14(1):250. PubMed PMC

Wrzodek C, Büchel F, Ruff M, et al. . Precise generation of systems biology models from KEGG pathways. BMC Syst Biol 2013;7(1):15. PubMed PMC

Rodriguez N, Pettit J-B, Dalle Pezze P, et al. . The systems biology format converter. BMC Bioinformatics 2016;17(1):154. PubMed PMC

Bergman FT. SBML Layout Viewer. http://sysbioapps.dyndns.org/Layout (16 November 2018, date last accessed).

Hoksza D, Gawron P, Ostaszewski M, et al. . MolArt: a molecular structure annotation and visualization tool. Bioinformatics 2018;34(23):4127–8. PubMed PMC

MINERVA team. MINERVA API documentation. https://minerva.pages.uni.lu/doc/api/12.2/index/ (16 January 2019, date last accessed).

MINERVA team. MINERVA conversion API documentation. https://minerva.pages.uni.lu/doc/api/12.2/converter/ (16 January 2019, date last accessed).

Bergmann FT, Adams R, Moodie S, et al. . COMBINE archive and OMEX format: one file to share all information to reproduce a modeling project. BMC Bioinformatics 2014;15(1):369. PubMed PMC

Visualization of automatically combined disease maps and pathway diagrams for rare diseases