Letter

Wiring diagrams in biology: towards the standardized

representation of biological information
Astrid Junker1, Anatoly Sorokin2, Tobias Czauderna1, Falk Schreiber1,3, and
Alexander Mazein4
1

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

The growing complexity of experimental datasets

requires a uniform representation of knowledge for accurate and efficient information exchange. The Systems
Biology Graphical Notation (SBGN) [1] standardizes the
graphical representation of biological networks. We introduce SBGN bricks as a way to represent typical
biological patterns in networks. SBGN bricks should
serve as a tool for biologists to draw networks quickly
that can then easily be interpreted, used, and altered by
other scientists.
SBGN enables scientists to denote their knowledge in a
structured and unambiguous way; a prerequisite for
knowledge transfer in all areas of biology. Furthermore,
SBGN provides different levels of detail and highlights
missing information, giving feedback to the scientist in the
laboratory. Several studies [2,3] and databases [46] have
applied SBGN for network representation using SBGN
supporting tools [7], thereby facilitating the understanding
and the communication of their results and contents in the
community.
The three complementary languages of SBGN, Process
Descriptions (PD), Entity Relationships (ER), and Activity
Flows (AF) (www.sbgn.org), represent biological networks
at different levels of granularity. PD [8] represents the
transition of entities, such as proteins or genes, from one
state to another. Processes consist of three parts: one or
more source entities, the process node, and one or more
product entities. PD most suitably represents mechanistic
details and temporal aspects of biological events, as in
biochemical networks.
ER [9] focuses on interactions between entities and their
influences on other entities. Relations between entities can
result in an interaction, a product entity, or the assignment
of variable values to entities that determine their location
or status. ER does not consider temporal aspects and only
ambiguously describes underlying mechanisms, therefore
being suitable for representation of protein-interaction
networks.
AF [10] represents the simplest level of detail and is
comparable to conventional arrow diagrams. AF focuses on
biological activities, represented by activity nodes. Modulation arcs show the influence between activities. Sequential influences between different activities are used to
Corresponding author: Junker, A. (junkera@ipk-gatersleben.de).

represent networks of functional genomics or signaling

networks.
All SBGN glyphs used in each language can be
found at www.sbgn.org. Using the example of transcription factor (TF)-mediated regulation of transcription,
Figure 1 exemplifies the features of the SBGN languages.
SBGN bricks: from patterns to networks
SBGN bricks represent a template-based approach for
learning and applying SBGN. Various bricks represent
recurring biological patterns in all languages of SBGN,
thereby enabling users to start drawing SBGN maps
directly without needing to know all of the specifications.
An initial SBGN bricks dictionary is available for
download in the SBGN-ML format at http://sbgnbricks.
sourceforge.net.
Figure 1 shows how SBGN bricks can be used to assemble a gene regulatory network comprised genes and their
corresponding transcripts and proteins in a cell. The interactions between these entities determine the rates of gene
transcription. Each mRNA will be translated into the
protein, which, in the case of TF, activates or inhibits
further regulatory cascades.
The respective transcription brick (Figure 1) refers to
transcription and its regulation by TF, binding to the
genomic DNA, thereby activating transcription resulting
in the target gene mRNA. All three languages of SBGN can
represent the transcription pattern. PD (Figure 1a) represents transcription by the production of mRNA from unspecified substrates and the stimulation of this process by
the complex of TF and the genomic DNA fragment corresponding to the target gene X. ER (Figure 1b) requires that
only the relation between transcription factor and target
gene X can lead to the existence of the corresponding
mRNA X. AF (Figure 1c) shows the flow of activities from
transcriptional regulators over the DNA-binding complex
to the mRNA X.
Using the PD language, three bricks have been assembled resulting in a gene regulatory network (Figure 1d).
This network comprises a two-step regulatory cascade with
TF1 stimulating the transcription of X, a TF-encoding gene
(transcription brick) that is translated into the TF2 protein
(translation brick). TF2 in turn regulates the transcription
of another gene Y (transcription brick).
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Trends in Biotechnology November 2012, Vol. 30, No. 11

Biological paern
Transcripon

SBGN bricks
(a)

Direct regulaon of a target gene by a

transcripon factor (promoter binding)

(b)

Process descripons
(PD)

(c)

Enty relaonships
(ER)

Acvity ows (AF)

ct:gene

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

Assembly of SBGN PD bricks

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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basic biological patterns, available at http://sbgnbricks.

sourceforge.net.
In the years to come, comprehensive ontology-based
structuring of SBGN bricks, as initialized here using the
Gene Ontology (GO), will provide a classification of typical
biological patterns. Furthermore, designing a catalog of
common mathematical descriptions based on SBGN bricks

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.

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0167-7799/$ see front matter 2012 Elsevier Ltd. All rights reserved.
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