Motivation: Since the knowledge about processes in living cells is increasing, modelling and simulation techniques are used to get new insights into these complex processes. During the last few ...years, the SBML file format has gained in popularity and support as a means of exchanging model data between the different modelling and simulation tools. In addition to specifying the model as a set of equations, many modern modelling tools allow the user to create and to interact with the model in the form of a reaction graph. Unfortunately, the SBML file format does not provide for the storage of this graph data along with the mathematical description of the model. Results: Therefore, we developed an extension to the SBML file format that makes it possible to store such layout information which describes position and size of objects in the graphical representation. Availability: The complete specification can be found on ( (SBML Layout Extension documentation, 2005). Additionally, a complete implementation exists as part of libSBML (2006, ). Contact:Ralph.Gauges@eml-r.villa-bosch.de Supplementary information: Supplementary data are available on Bioinformatics online.
To study complex biochemical reaction networks in living cells researchers more and more rely on databases and computational methods. In order to facilitate computational approaches, visualisation ...techniques are highly important. Biochemical reaction networks, e.g. metabolic pathways are often depicted as graphs and these graphs should be drawn dynamically to provide flexibility in the context of different data. Conventional layout algorithms are not sufficient for every kind of pathway in biochemical research. This is mainly due to certain conventions to which biochemists/biologists are used to and which are not in accordance to conventional layout algorithms. A number of approaches has been developed to improve this situation. Some of these are used in the context of biochemical databases and make more or less use of the information in these databases to aid the layout process. However, visualisation becomes also more and more important in modelling and simulation tools which mostly do not offer additional connections to databases. Therefore, layout algorithms used in these tools have to work independently of any databases. In addition, all of the existing algorithms face some limitations with respect to the number of edge crossings when it comes to larger biochemical systems due to the interconnectivity of these. Last but not least, in some cases, biochemical conventions are not met properly.
Out of these reasons we have developed a new algorithm which tackles these problems by reducing the number of edge crossings in complex systems, taking further biological conventions into account to identify and visualise cycles. Furthermore the algorithm is independent from database information in order to be easily adopted in any application. It can also be tested as part of the SimWiz package (free to download for academic users at 1).
The new algorithm reduces the complexity of pathways, as well as edge crossings and edge length in the resulting graphical representation. It also considers existing and further biological conventions to create a drawing most biochemists are familiar with. A lot of examples can be found on 2.
The Systems Biology Graphical Notation Le Novère, Nicolas; Hucka, Michael; Mi, Huaiyu ...
Nature biotechnology,
08/2009, Volume:
27, Issue:
8
Journal Article
Peer reviewed
Open access
Circuit diagrams and Unified Modeling Language diagrams are just two examples of standard visual languages that help accelerate work by promoting regularity, removing ambiguity and enabling software ...tool support for communication of complex information. Ironically, despite having one of the highest ratios of graphical to textual information, biology still lacks standard graphical notations. The recent deluge of biological knowledge makes addressing this deficit a pressing concern. Toward this goal, we present the Systems Biology Graphical Notation (SBGN), a visual language developed by a community of biochemists, modelers and computer scientists. SBGN consists of three complementary languages: process diagram, entity relationship diagram and activity flow diagram. Together they enable scientists to represent networks of biochemical interactions in a standard, unambiguous way. We believe that SBGN will foster efficient and accurate representation, visualization, storage, exchange and reuse of information on all kinds of biological knowledge, from gene regulation, to metabolism, to cellular signaling.
Transforming growth factor β (TGF-β) ligands activate a signaling cascade with multiple cell context dependent outcomes. Disruption or disturbance leads to variant clinical disorders. To develop ...strategies for disease intervention, delineation of the pathway in further detail is required. Current theoretical models of this pathway describe production and degradation of signal mediating proteins and signal transduction from the cell surface into the nucleus, whereas feedback loops have not exhaustively been included.
In this study we present a mathematical model to determine the relevance of feedback regulators (Arkadia, Smad7, Smurf1, Smurf2, SnoN and Ski) on TGF-β target gene expression and the potential to initiate stable oscillations within a realistic parameter space. We employed massive sampling of the parameters space to pinpoint crucial players for potential oscillations as well as transcriptional product levels. We identified Smad7 and Smurf2 with the highest impact on the dynamics. Based on these findings, we conducted preliminary time course experiments.
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► We present a mathematical model to determine the relevance of feedback loops in the TGF-β signaling. ► Our computational analysis indicated that oscillations are possible under realistic conditions. ► Smad7 and Smurf1/2 have the strongest potential to act as negative feedback regulators. ► Ski, SnoN, SARA, Arkadia have a high potential to also act as positive feedback mechanisms. ► Preliminary experimental data revealed a more dynamic behavior than the simple on-off mechanism.
The basic linear treatment of sequence comparisons limits the ability of contemporary sequence alignment algorithms to detect non-order-conserving recombinations. Here, we introduce the algorithm ...combAlign which addresses the assessment of pairwise sequence similarity on non-order-conserving recombinations on a large scale. Emphasizing a two-level approach, combAlign first detects locally well conserved subsequences in a target and a source sequence. Subsequently, the relative placement of alignments is mapped to a graph. Concatenating local alignments to reassemble the target sequence to the fullest extent, the maximum scoring path through the graph denotes the best attainable combAlignment. Parameters influencing this process can be set to meet the user's specific demands. combAlign is applied to examples demonstrating the possibility to reflect evolutionary kinship of proteins even if their domains and motifs are strongly rearranged.
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