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Using process diagrams for the graphical representation of biological networks

Abstract

With the increased interest in understanding biological networks, such as protein-protein interaction networks and gene regulatory networks, methods for representing and communicating such networks in both human- and machine-readable form have become increasingly important. Although there has been significant progress in machine-readable representation of networks, as exemplified by the Systems Biology Mark-up Language (SBML) (http://www.sbml.org) issues in human-readable representation have been largely ignored. This article discusses human-readable diagrammatic representations and proposes a set of notations that enhances the formality and richness of the information represented. The process diagram is a fully state transition–based diagram that can be translated into machine-readable forms such as SBML in a straightforward way. It is supported by CellDesigner, a diagrammatic network editing software (http://www.celldesigner.org/), and has been used to represent a variety of networks of various sizes (from only a few components to several hundred components).

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Figure 1: A pathway in different graphical notations.
Figure 2: Proposed set of symbols for representing biological networks with process diagrams.
Figure 3: Representing combinatorial states.
Figure 4: Syntax of index for category-II reduced notation and correspondence with the standard process diagram notation.

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Acknowledgements

We thank Akiya Jouraku for validating syntax for reduced notation, members of the Systems Biology Institute (SBI) for useful discussions and the PANTHER pathway team at Applied Biosystems for detailed feedback and discussions. This research is supported, in part, by the ERATO-SORST Program to SBI, Japan Science and Technology Agency, an international grant for international standard formation to SBI from New Energy Development Organization, the Genome Network Project to SBI by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), the special coordinated funding and the 21st century Center of Excellence program to Keio University by MEXT.

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Correspondence to Hiroaki Kitano.

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Supplementary information

Supplementary Fig. 1

Definition of the Process Diagram. (PDF 92 kb)

Supplementary Fig. 2

An example of G-protein Coupled Receptor Activation-Deactivation Cycle. (PDF 150 kb)

Supplementary Fig. 3

An example of NF-κB related interactions. (PDF 217 kb)

Supplementary Fig. 4

Structure of Complex. (PDF 147 kb)

Supplementary Fig. 5

Transcription Process. (PDF 1346 kb)

Supplementary Fig. 6

Equivalence of Standard Notation and Reduced Notation. (PDF 209 kb)

Supplementary Fig. 7

Limitations of Reduced Notation. (PDF 141 kb)

Supplementary Fig. 8

Mapping between the process diagram and Kohn notation. (PDF 89 kb)

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Kitano, H., Funahashi, A., Matsuoka, Y. et al. Using process diagrams for the graphical representation of biological networks. Nat Biotechnol 23, 961–966 (2005). https://doi.org/10.1038/nbt1111

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