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Leibniz Institute of Plant Genetics and Crop Plant Research Gatersleben (IPK), Corrensstrasse 3, D-06466 Gatersleben, Germany
Institute of Cell Biophysics RAS, Institutskaya str. 4, Pushcino, Moscow region, 142290, Russia
3
Institute of Computer Science, Martin Luther University Halle-Wittenberg, Von-Seckendorff-Platz 1, D-06120 Halle, Germany
4
Division of Pathway Medicine, University of Edinburgh, Chancellors Building, Little France Crescent, Edinburgh, EH16 4SB, UK
2
Letter
Biological paern
Transcripon
SBGN bricks
(a)
(b)
Process descripons
(PD)
(c)
Enty relaonships
(ER)
mt: prot
TF
GO:0065004 (protein-DNA
complex assembly)
mt:prot
ct:gene
TF
ct:gene
ct:mRNA
AND
GO:0006355 (regulaon of
transcripon, DNA-dependent)
GO:0009299 (mRNA
mt:prot
ct:gene
TF
TF_X
transcripon)
mt:prot
GO:0006351 (transcripon,
TF
ct:mRNA
DNA-dependent)
T
ct:mRNA
Biological network
Gene regulatory
network
ct:mRNA
(d)
X
ct:gene
mt:prot
TF1
mt:prot
TF1
ct: gene
mt:prot
X=TF2
ct:gene
mt:prot
ct: gene
TF2
ct:mRNA
TRENDS in Biotechnology
Figure 1. Systems Biology Graphical Notation (SBGN) bricks for the transcription pattern, recurring in, for example, gene regulatory networks. All three languages of SBGN
are suitable for the representation of the transcription pattern. Different Gene Ontology (GO) terms are assigned to the transcription brick in order to specify the described
biological process independent of the SBGN language. In the following description of the transcription bricks, names of the SBGN glyphs as they are specified in the
technical specifications of the three languages (www.sbgn.org) are indicated by apostrophes, for example, macromolecule for the macromolecule glyph. (a) Process
Descriptions: during direct gene regulation, a transcription factor (TF) complexes the target gene promoter as a piece of genomic DNA. The TF protein is a macromolecule
with the material type protein (mt:prot), whereas the promoter of gene X is given as a nucleic acid feature with the conceptual type gene (ct:gene). The complex of both
regulator and target gene promoter triggers the process of transcription. The connecting arc necessary stimulation is applied to indicate that this stimulation by the
regulatortarget gene complex is necessary for the transcription process to take place. The messenger of target gene X as the product of the transcription process is
represented by a nucleic acid feature with the conceptual type mRNA (ct:mRNA). The unspecified source symbol is used to represent the large number of different
substrates of a transcription process (e.g., trinucleotides) which should not be specified in detail. (b) Entity Relationships: a TF entity interacts with a target gene genomic
DNA entity X. The target gene mRNA entity comes into existence only if this interaction takes place as indicated by the assignment of a variable value with the label T for
true. The connecting arc necessary stimulation is applied to indicate that the interaction of regulator and target is necessary for the transcription to take place. All entities
carry units of information with the label indicating the material (mt:prot) or conceptual types (ct:gene, ct:mRNA). (c) Activity Flows: the activities of a TF and its target gene
DNA X necessarily stimulate the activity of the target gene mRNA X. The identities of genomic fragments of DNA or RNA as nucleic acid features is represented by the
shape of the unit of information and the conceptual types as labels in the unit of information (ct:gene, ct:mRNA). The connecting arc necessary stimulation is applied to
indicate that the stimulation by both the activities of TF and target gene DNA is necessary for the target gene mRNA activity. (d) Assembly of Process Description bricks into
a gene regulatory network. Two transcription bricks (green) and one translation brick (purple) have been assembled in order to represent a two-step regulatory cascade. The
target gene X of TF1 encodes TF2, which in turn regulates the transcription of gene Y. Using SBGN bricks basically requires two hands-on steps: first, the user has to adapt
the glyph labels according to individual purposes; and second, glyph merging has to be performed. Here, merged glyphs that belong to both connected SBGN bricks are
indicated by different fill and frame colors. The mRNA of gene X (frame: green; filling: purple) is the product of the transcription process and the substrate of the translation
process, and analogously the protein X (frame: purple; filling: green), which corresponds to TF2, is the product of the translation process and the regulator of transcription
of gene Y.
Concluding remarks
SBGN transfers the principle of wiring diagrams in engineering to biology, and especially to biotechnology as the
engineering of biological systems. By analogy with the
concept of reusable patterns, which has been proven to
be effective in areas from architecture to software engineering, SBGN bricks provide templates for a wide range of
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Letter
will contribute to semiautomatic model assembly using
SBGN bricks as a visual guide for model creation. Strict
and unambiguous definitions of SBGN bricks are key to
understanding the biological meaning of models as a prerequisite for mathematical simulations and consequent
modifications of the underlying systems, thereby elucidating novel targets for biotechnology.
Acknowledgments
We thank Jan Huge, Hendrik Rohn, and Anja Hartmann for helpful
suggestions.
References
1 Le Nove`re, N. et al. (2009) The Systems Biology Graphical Notation.
Nat. Biotechnol. 27, 735741
2 Rogers, L.D. et al. (2011) Phosphoproteomic analysis of Salmonellainfected cells identifies key kinase regulators and SopB-dependent host
phosphorylation events. Sci. Signal. 4, rs9
3 Thingnes, J. et al. (2012) Towards a quantitative understanding of the
MITF-PIAS3-STAT3 connection. BMC Syst. Biol. 6, 11
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