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Creating interactive, web-based and data-enriched maps with the Systems Biology Graphical Notation

Abstract

The Systems Biology Graphical Notation (SBGN) is an emerging standard for the uniform representation of biological processes and networks. By using examples from gene regulation and metabolism, this protocol shows the construction of SBGN maps by either manual drawing or automatic translation using the tool SBGN-ED. In addition, it discusses the enrichment of SBGN maps with different kinds of -omics data to bring numerical data into the context of these networks in order to facilitate the interpretation of experimental data. Finally, the export of such maps to public websites, including clickable images, supports the communication of results within the scientific community. With regard to the described functionalities, other tools partially overlap with SBGN-ED. However, currently, SBGN-ED is the only tool that combines all of these functions, including the representation in SBGN, data mapping and website export. This protocol aims to assist scientists with the step-by-step procedure, which altogether takes 90 min.

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Figure 1: Workflow of the creation of interactive, web-based and data-enriched maps using SBGN.
Figure 2: The SBGN Process Description (PD) notation.
Figure 3: Screenshot of the SBGN-ED desktop.
Figure 4: Regulatory interactions between four master regulators of Arabidopsis seed development: LEC1, LEC2, FUS3 and ABI3.
Figure 5
Figure 6: Screenshot of a mapping table.
Figure 7: Manually edited LEC1/AFL-B3 regulatory network of Arabidopsis seed transcription factors enriched by time-resolved expression data.
Figure 8
Figure 9: Metabolic network of the TCA cycle taken from the MetaCrop database, enriched by metabolic measurement data.
Figure 10: Example website.

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References

  1. Le Novere, N. et al. The systems biology graphical notation. Nat. Biotechnol. 27, 735–741 (2009).

    Article  CAS  Google Scholar 

  2. Junker, A., Hartmann, A., Schreiber, F. & Baumlein, H. An engineer's view on regulation of seed development. Trends Plant Sci. 15, 303–307 (2010).

    Article  CAS  Google Scholar 

  3. Caron, E. et al. A comprehensive map of the mTOR signaling network. Mol. Syst. Biol. 6, 453 (2010).

    Article  Google Scholar 

  4. Kierzek, A.M., Zhou, L. & Wanner, B.L. Stochastic kinetic model of two component system signalling reveals all-or-none, graded and mixed mode stochastic switching responses. Mol. Biosyst. 6, 531–542 (2010).

    Article  CAS  Google Scholar 

  5. Jansson, A. & Jirstrand, M. Biochemical modeling with systems biology graphical notation. Drug Discov. Today 15, 365–370 (2010).

    Article  CAS  Google Scholar 

  6. Funahashi, A. et al. CellDesigner 3.5: a versatile modeling tool for biochemical networks. Proceedings of the IEEE 96, 1254–1265 (2008).

    Article  Google Scholar 

  7. Zinovyev, A., Viara, E., Calzone, L. & Barillot, E. BiNoM: a Cytoscape plugin for manipulating and analyzing biological networks. Bioinformatics 24, 876–877 (2008).

    Article  CAS  Google Scholar 

  8. van Iersel, M.P. et al. Presenting and exploring biological pathways with PathVisio. BMC Bioinformatics 9, 399 (2008).

    Article  Google Scholar 

  9. Czauderna, T., Klukas, C. & Schreiber, F. Editing, validating and translating of SBGN maps. Bioinformatics 26, 2340–2341 (2010).

    Article  CAS  Google Scholar 

  10. Gehlenborg, N. et al. Visualization of omics data for systems biology. Nat. Methods 7, S56 S (2010).

    Article  CAS  Google Scholar 

  11. Suderman, M. & Hallett, M. Tools for visually exploring biological networks. Bioinformatics 23, 2651–2659 (2007).

    Article  CAS  Google Scholar 

  12. Sorokin, A. et al. The pathway editor: a tool for managing complex biological networks. IBM J. Res. Dev. 50, 561–573 (2006).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Schreiber, F. et al. MetaCrop 2.0: managing and exploring information about crop plant metabolism. Nucleic Acid Res. published online, doi:10.1093/nar/GKR1004 (15 November, 2011).

    Article  CAS  Google Scholar 

  15. Moodie, S., Le Novère, N., Emek, D., Huaiyu, M. & Villeger, A. Systems biology graphical notation: process description language level 1V3. Nature Precedings published online, doi:10.1038/npre.2011.3721.4 (17 February, 2011).

  16. Grafahrend-Belau, E. et al. MetaCrop: a detailed database of crop plant metabolism. Nucleic Acids Res. 36, D954–D958 (2008).

    Article  CAS  Google Scholar 

  17. Zimmermann, P., Hirsch-Hoffmann, M., Hennig, L. & Gruissem, W. GENEVESTIGATOR. Arabidopsis microarray database and analysis toolbox. Plant Physiol. 136, 2621–2632 (2004).

    Article  CAS  Google Scholar 

  18. Junker, B.H. et al. Temporally regulated expression of a yeast invertase in potato tubers allows dissection of the complex metabolic phenotype obtained following its constitutive expression. Plant Mol. Biol. 56, 91–110 (2004).

    Article  CAS  Google Scholar 

  19. Stone, S.L. et al. Arabidopsis LEAFY COTYLEDON2 induces maturation traits and auxin activity: implications for somatic embryogenesis. Proc. Natl. Acad. Sci. USA 105, 3151–3156 (2008).

    Article  CAS  Google Scholar 

  20. To, A. et al. A network of local and redundant gene regulation governs Arabidopsis seed maturation. Plant Cell 18, 1642–1651 (2006).

    Article  CAS  Google Scholar 

  21. Villeger, A.C., Pettifer, S.R. & Kell, D.B. Arcadia: a visualization tool for metabolic pathways. Bioinformatics 26, 1470–1471 (2010).

    Article  CAS  Google Scholar 

  22. Chandran, D., Bergmann, F.T. & Sauro, H.M. Athena: modular CAM/CAD software for synthetic biology. arXiv.org published online, arXiv:0902.2598v1 (2009).

  23. Chabrier-Rivier, N., Fages, F. & Soliman, S. in Computational Methods in Systems Biology. Lecture Notes in Computer Science Vol. 3082 (eds. Danos, V. & Schachter, V.) 172–191 (Springer-Verlag, 2005).

  24. Olivier, B.G. & Snoep, J.L. Web-based kinetic modelling using JWS Online. Bioinformatics 20, 2143–2144 (2004).

    Article  CAS  Google Scholar 

  25. Battke, F., Symons, S. & Nieselt, K. Mayday—integrative analytics for expression data. BMC Bioinformatics 11 (2010).

  26. Wegner, K. et al. The NetBuilder' project: development of a tool for constructing, simulating, evolving, and analysing complex regulatory networks. BMC Syst. Biol. 1, P72 (2007).

    Article  Google Scholar 

  27. Deckard, A., Bergmann, F.T. & Sauro, H.M. Supporting the SBML layout extension. Bioinformatics 22, 2966–2967 (2006).

    Article  CAS  Google Scholar 

  28. Lammers, C.R. et al. Connecting parts with processes: SubtiWiki and SubtiPathways integrate gene and pathway annotation for Bacillus subtilis. Microbiology 156, 849–859 (2010).

    Article  CAS  Google Scholar 

  29. Reyes Palomares, A. et al. Systems biology metabolic modeling assistant: an ontology-based tool for the integration of metabolic data in kinetic modeling. Bioinformatics 25, 834–835 (2009).

    Article  CAS  Google Scholar 

  30. Dilek, A., Belviranli, M.E. & Dogrusoz, U. VISIBIOweb: visualization and layout services for BioPAX pathway models. Nucleic Acids Res. 38, W150–W154 (2010).

    Article  CAS  Google Scholar 

  31. Elowitz, M. & Leibler, S. A synthetic oscillatory network of transcriptional regulators. Nature 403, 335–338 (2000).

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to J. Hüge and B. Junker for helpful discussions and advice.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed extensively to the work presented in this paper. A.J. and H.R. wrote the paper. T.C. and C.K. wrote the code. A.H. developed the tutorial. A.H., T.C. and F.S. edited the manuscript. F.S. supervised the project and gave conceptual advice.

Corresponding author

Correspondence to Astrid Junker.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Tutorial

Creating interactive, web-based and data-enriched maps using the Systems Biology Graphical Notation. (PDF 10646 kb)

Supplementary Data 1

LEC1/AFL-B3 regulatory network. This file represents the result of the manual drawing process (Steps 9Ai-xxiv). It can directly be loaded into SBGN-ED for further layouting or data mapping. (ZIP 1 kb)

Supplementary Data 2

TCA cycle metabolic network. This file represents the result of the import of a SBGN style metabolic network from the MetaCrop database (Steps 9Bi-iii). It can directly be loaded into SBGN-ED for further layouting or data mapping. (ZIP 2 kb)

Supplementary Data 3

Excel template with expression data. This template file contains expression data obtained from the Genevestigator database for four transcription factors of the LEC1/AFL-B3 regulatory network. It can directly be used for upload into SBGN-ED and for mapping onto the LEC1/AFL-B3 regulatory network as described in Steps 10Ai-x. (XLS 29 kb)

Supplementary Data 4

Mapping table for mapping of expression data. This mapping table provides alternative IDs (AGI gene IDs for Arabidopsis) for the mapping of expression data on the LEC1/AFL-B3 regulatory network which contains only the gene names. (XLS 26 kb)

Supplementary Data 5

Regulatory network mapping. This file shows the LEC1/AFL-B3 regulatory network enriched by expression data as the result of Steps 10Ai-x. It can directly be loaded into SBGN-ED for further layouting or data mapping. (ZIP 3 kb)

Supplementary Data 6

Excel template with metabolic data. This template file contains metabolite measurement data obtained from literature. It can directly be used for upload into SBGN-ED and for mapping onto the TCA cycle metabolic network as described in Steps 10Bi-iii. (XLS 76 kb)

Supplementary Data 7

Metabolic pathway mapping. This file shows the TCA cycle metabolic network enriched by metabolite data as the result of steps 10Bi-iii. It can directly be loaded into SBGN-ED for further layouting or data mapping. (ZIP 8 kb)

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Junker, A., Rohn, H., Czauderna, T. et al. Creating interactive, web-based and data-enriched maps with the Systems Biology Graphical Notation. Nat Protoc 7, 579–593 (2012). https://doi.org/10.1038/nprot.2012.002

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