Editing, validating and translating of SBGN maps

Motivation: The recently proposed Systems Biology Graphical Notation (SBGN) provides a standard for the visual representation of biochemical and cellular processes. It aims to support more efficient and accurate communication of biological knowledge between different research communities in the life sciences. However, to increase the use of SBGN, tools for editing, validating and translating SBGN maps are desirable

Novel developments in SBGN-ED and applications

Systems Biology Graphical Notation (SBGN, http://sbgn.org) [1] is an emerging standard for graphical representations of biochemical and cellular processes studied in systems biology. Three different views (Process Description, Entity Relationship, and Activity Flow) cover several aspects of the represented processes in different levels of detail. SBGN helps to communicate biological knowledge more efficient and accurate between different research communities in the life sciences. However, to support SBGN, methods and tools for editing, validating, and translating of SBGN maps are necessary.
We present methods for these tasks and novel developments in SBGN-ED (www.sbgn-ed.org) [2], a tool which allows to create all three types of SBGN maps from scratch, to validate these maps for syntactical and semantical correctness, to translate maps from the KEGG database into SBGN, and to export SBGN maps into several file and image formats. SBGN-ED is based on VANTED (Visualization and Analysis of NeTworks containing Experimental Data, http://www.vanted.org) [3].
As applications of SBGN and SBGN-ED we present furthermore MetaCrop (http://metacrop.ipk-gatersleben.de) [4], a database that summarizes diverse information about metabolic pathways in crop plants, and RIMAS (Regulatory Interaction Maps of Arabidopsis Seed Development, http://rimas.ipk-gatersleben.de) [5], an information portal that provides a comprehensive overview of regulatory pathways and genetic interactions during Arabidopsis embryo and seed development. 

[1] Le Novère, N. et al. (2009) The Systems Biology Graphical Notation. Nature Biotechnology, 27, 735-741.
[2] Czauderna, T., Klukas, C., Schreiber, F. (2010) Editing, validating, and translating of SBGN maps. Bioinformatics, 26 (18), 2340-2341.
[3] Junker, B.H., Klukas, C., Schreiber, F. (2006) VANTED: A system for advanced data analysis and visualization in the context of biological networks. BMC Bioinformatics, 7, 109+.
[4] Grafahrend-Belau, E., Weise, S., Koschützki, D., Scholz, U., Junker, B.H., Schreiber, F. (2008) MetaCrop - A detailed database of crop plant metabolism. Nucleic Acids Research, 36, D954-D958.
[5] Junker, A., Hartmann, A., Schreiber, F., Bäumlein, H. (2010) An engineer's view on regulation of seed development. Trends in Plant Science, 15(6), 303-307.
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NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps

Molecular biology knowledge can be systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist a number of maps of molecular interactions containing detailed description of various cell mechanisms. It is difficult to explore these large maps, to comment their content and to maintain them. Though there exist several tools addressing these problems individually, the scientific community still lacks an environment that combines these three capabilities together. NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. NaviCell combines three features: (1) efficient map browsing based on Google Maps engine; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting the community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of their interest in the context of signaling pathways and cross-talks between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive fashion due to an imbedded blogging system. NaviCell provides an easy way to explore large-scale maps of molecular interactions, thanks to the Google Maps and WordPress interfaces, already familiar to many users. Semantic zooming used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization meaningful to the user. In addition, NaviCell provides a framework for community-based map curation.Comment: 20 pages, 5 figures, submitte

Toward community standards and software for whole-cell modeling

Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate, comprehensive models of complex cells. Methods: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in SBML. Results: Our analysis revealed several challenges to representing WC models using the current standards. Conclusion: We, therefore, propose several new WC modeling standards, software, and databases. Significance:We anticipate that these new standards and software will enable more comprehensive models

Formalization of molecular interaction maps in systems biology; Application to simulations of the relationship between DNA damage response and circadian rhythms

Quantitative exploration of biological pathway networks must begin with a qualitative understanding of them. Often researchers aggregate and disseminate experimental data using regulatory diagrams with ad hoc notations leading to ambiguous interpretations of presented results. This thesis has two main aims. First, it develops software to allow researchers to aggregate pathway data diagrammatically using the Molecular Interaction Map (MIM) notation in order to gain a better qualitative understanding of biological systems. Secondly, it develops a quantitative biological model to study the effect of DNA damage on circadian rhythms. The second aim benefits from the first by making use of visual representations to identify potential system boundaries for the quantitative model. I focus first on software for the MIM notation - a notation to concisely visualize bioregulatory complexity and to reduce ambiguity for readers. The thesis provides a formalized MIM specification for software implementation along with a base layer of software components for the inclusion of the MIM notation in other software packages. It also provides an implementation of the specification as a user-friendly tool, PathVisio-MIM, for creating and editing MIM diagrams along with software to validate and overlay external data onto the diagrams. I focus secondly on the application of the MIM software to the quantitative exploration of the poorly understood role of SIRT1 and PARP1, two NAD+-dependent enzymes, in the regulation of circadian rhythms during DNA damage response. SIRT1 and PARP1 participate in the regulation of several key DNA damage-repair proteins and are the subjects of study as potential cancer therapeutic targets. In this part of the thesis, I present an ordinary differential equation (ODE) model that simulates the core circadian clock and the involvement of SIRT1 in both the positive and negative arms of circadian regulation. I then use this model is then used to predict a potential role for the competition for NAD+ supplies by SIRT1 and PARP1 leading to the observed behavior of primarily phase advancement of circadian oscillations during DNA damage response. The model further predicts a potential mechanism by which multiple forms of post-transcriptional modification may cooperate to produce a primarily phase advancement

PathVisio-Validator: a rule-based validation plugin for graphical pathway notations.

Purpose: The PathVisio-Validator plugin aims to simplify the task of producing biological pathway diagrams that follow graphical standardized notations, such as Molecular Interaction Maps or the Systems Biology Graphical Notation. This plugin assists in the creation of pathway diagrams by ensuring correct usage of a notation, and thereby reducing ambiguity when diagrams are shared amongst biologists. Rulesets needed in the validation process, can be generated for any graphical notation that a developer desires, using either Schematron or Groovy. The plugin also provides support for filtering validation results, validating on a subset of rules, and distinguishing errors and warnings. AVAILABILITY: The PathVisio-Validator plugin works with versions of PathVisio 2.0.11 and later on Windows, Mac OS X, and Linux. The plugin along with the instructions, example rulesets for Groovy and Schematron, and Java source code can be downloaded at http://pathvisio.org/wiki/PathVisioValidatorHelp. The software is developed under the open source Apache 2.0 License and is freely available for both commercial and academic use. CONTACT: [email protected] or [email protected]

Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)--in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics). Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools

A formal MIM specification and tools for the common exchange of MIM diagrams: an XML-Based format, an API, and a validation method

<p>Abstract</p> <p>Background</p> <p>The Molecular Interaction Map (MIM) notation offers a standard set of symbols and rules on their usage for the depiction of cellular signaling network diagrams. Such diagrams are essential for disseminating biological information in a concise manner. A lack of software tools for the notation restricts wider usage of the notation. Development of software is facilitated by a more detailed specification regarding software requirements than has previously existed for the MIM notation.</p> <p>Results</p> <p>A formal implementation of the MIM notation was developed based on a core set of previously defined glyphs. This implementation provides a detailed specification of the properties of the elements of the MIM notation. Building upon this specification, a machine-readable format is provided as a standardized mechanism for the storage and exchange of MIM diagrams. This new format is accompanied by a Java-based application programming interface to help software developers to integrate MIM support into software projects. A validation mechanism is also provided to determine whether MIM datasets are in accordance with syntax rules provided by the new specification.</p> <p>Conclusions</p> <p>The work presented here provides key foundational components to promote software development for the MIM notation. These components will speed up the development of interoperable tools supporting the MIM notation and will aid in the translation of data stored in MIM diagrams to other standardized formats. Several projects utilizing this implementation of the notation are outlined herein. The MIM specification is available as an additional file to this publication. Source code, libraries, documentation, and examples are available at <url>http://discover.nci.nih.gov/mim</url>.</p