VisBOL: Web-Based Tools for Synthetic Biology Design Visualization

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VisBOL: Web-based tools for synthetic biology design visualization James Alastair McLaughlin, Matthew Pocock, Goksel Misirli, Curtis Madsen, and Anil Wipat ACS Synth. Biol., Just Accepted Manuscript • DOI: 10.1021/acssynbio.5b00244 • Publication Date (Web): 25 Jan 2016 Downloaded from http://pubs.acs.org on January 26, 2016

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ACS Synthetic Biology

VisBOL: Web-based tools for synthetic biology design visualization James Alastair McLaughlin,‡ Matthew Pocock,§ G¨oksel Mısırlı,‡ Curtis Madsen,‡ and Anil Wipat∗,‡ ‡School of Computing Science, Newcastle University, UK §Turing Ate My Hamster Ltd E-mail: [email protected]

Running header VisBOL: Web-based tools for synthetic biology design visualization

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Abstract VisBOL is a Web-based application that allows the rendering of genetic circuit designs, enabling synthetic biologists to visually convey designs in SBOL visual format. VisBOL designs can be exported to formats including PNG and SVG images to be embedded in Web pages, presentations and publications. The VisBOL tool enables the automated generation of visualizations from designs specified using the Synthetic Biology Open Language (SBOL) version 2.0, as well as a range of well-known bioinformatics formats including GenBank and Pigeoncad notation. VisBOL is provided both as a user accessible website and as an open-source (BSD) JavaScript library that can be used to embed diagrams within other content and software.

Keywords Synthetic biology, visualization, Synthetic Biology Open Language, genetic circuits, SBOL Visual

Introduction Visual depictions have always been an important tool in the design of biological systems, from high-level whiteboard sketches to detailed technical drawings. Consequently, a graphical notation has evolved over time to convey the features of genetic circuit designs, using genetic feature such as promoters, ribosome binding sites, coding sequences, and terminators. This notation is still informal, and varies widely among biologists; for example, while some use a “hairpin loop” symbol to represent a terminator (1 ), others might instead draw a “T” shape (2 ) or a circle (3 ). Although variation among design notation is less important for human communication, the continued focus of synthetic biology on developing a well-defined, standardised, engineering approach requires that designs must be unambiguous at every stage of the design-build2


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and presenting a significant barrier to the adoption of SBOL Visual. Here we present a system for genetic circuit visualization using SBOL, including a freely available open source library and publicly accessible Web application for the visualization of SBOL designs.

Results and discussion

Figure 2: The VisBOL Design Visualizer, showing the design source (left) and the resulting visualization (right). The user is able to select a design source format and edit the design source in the left pane, and the visualization will be updated automatically on the right. In this example, a visualization of a LacI/TetR toggle switch generated from an SBOL2 document is shown. The three SBOL2 modules are shown first as individual components, and then as a composed backbone.

We have developed VisBOL, available at http://github.com/visbol under the BSD opensource license. A demonstration instance of the VisBOL design visualizer is available at http://visbol.org. VisBOL supports visualization of designs using the SBOL Visual standard

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(4 ) from sources including SBOL versions 1 (9 ) and 2 (10 ), pigeoncad (5 ) notation, GenBank (11 ) records, and a JSON (12 ) display list format. The user interface (Figure 2) shows the VisBOL user interface, which consists of two split panes. The left pane contains the source for the design, with a series of tabs allowing the user to choose from SBOL, Pigeoncad, GenBank, and display list format. When the source is modified, the visualization is updated automatically in the right pane, which provides a tab to display the visualization and a tab to download an image as Scalable Vector Graphic (13 ) or PNG. The display list tab leverages an extensible JSON display list format, acting as an intermediate between source representation and the rendering pipeline to enable color, style, and rendering annotations to be applied. The use of a display list format separates the interpretation of source design formats from the rendering of designs, enabling both new design formats and new visualisation strategies to be implemented distinctly. Designs generated from any source format can be viewed as a display list by switching to the display list tab at any time. As VisBOL is built on open Web technology, it is easily reusable, enabling interactive VisBOL designs to be embedded in existing Web page content such as part repositories, lab websites, and blogs. The visualisation technology is written entirely in JavaScript and runs locally in the Web browser, which provides two major advantages. Firstly, there is no requirement of any server-side software, so the visualiser can easily be embedded in frontend content without any further configuration. Secondly, the rendering process is entirely dynamic: changes to the design and renderer parameters are visible immediately, without a page reload or form submission. The VisBOL renderer generates SVG images to ensure that exported visualizations can be displayed at any resolution without loss of quality. SVG is a widely supported and versatile format, and SVG files can be converted to be displayed and edited in media such as PowerPoint presentations using readily available open-source software.

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VisBOL also provides a modular font system to allow the dynamic addition of new individual glyphs or entire glyph sets. As the SBOL Visual standard continues to evolve, this modularity will enable fast prototyping of new glyph ideas while leveraging the existing rendering infrastructure. The design visualizer is not only a user accessible service, but also embeddable in other content as a self-contained rendering toolkit. This enables VisBOL to be re-used in further software, so that any Web-based tool with SBOL support can add SBOL Visual visualization capabilities. An example usage of the library is available at http://visbol.org/design. Whilst VisBOL provides an open-source foundation for genetic circuit visualization, and there is scope for future research and development. For example, the SBOL version 2 standard defines the concept of modules, which serve as a top-level container for circuit components. VisBOL does not yet support rendering of modules. The automated visualization of modules and their relationships opens some interesting questions both regarding algorithms for layout, and more conceptual questions such as how to best present a graphical overview while maintaining a sufficient level of detail. Furthermore, there are limitations with the rendering of regulatory arcs in designs. Since SBOL provides no layout information, VisBOL calculates a route for arcs automatically using a variation of the A* path search algorithm (14 ). While this approach generates satisfactory results in many cases, VisBOL would benefit from a hinting mechanism whereby the user would be able to suggest a more visually appealing route, orientation, and direction. Finally, there is a possibility of adding “drag and drop” interactivity to the design visualizer, which would enable the development of a computer-aided design tool for the composition of genetic circuits. As VisBOL already provides the rendering infrastructure and user interactivity is straightforward in the Web browser, this would be a logical next step and a useful addition to the SBOL toolkit. To summarise, we have created an open-source software library that greatly simplifies the adoption of SBOL Visual as a graphical notation for genetic circuit design, and provides

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an infrastructure built on open Web technologies to facilitate future development in this area. We have demonstrated the use of this software library in a publicly available Web application, integrating the SBOL and SBOL Visual standards to make a user-friendly tool for the depiction of designs.

Acknowledgement The authors thank the SBOL Visual working group, and FUJIFILM DioSynth Technologies. G.M. and A.W. are supported by the Engineering and Physical Sciences Research Council grant EP/J02175X/1.

References 1. Van Assche, E., Van Puyvelde, S., Vanderleyden, J., and Steenackers, H. P. (2015) RNAbinding proteins involved in post-transcriptional regulation in bacteria. Front. Microbiol. 6. 2. Brophy, J. A., and Voigt, C. A. (2014) Principles of genetic circuit design. Nat. Methods 11, 508–520. 3. Kushwaha, M., and Salis, H. M. (2015) A portable expression resource for engineering cross-species genetic circuits and pathways. Nat. Commun. 6 . 4. Quinn, J., Beal, J., Bhatia, S., Cai, P., Chen, J., Clancy, K., Hillson, N., Galdzicki, M., Maheshwari, A., and Umesh, P. Synthetic Biology Open Language Visual (SBOL Visual); 2013. 5. Bhatia, S., and Densmore, D. (2013) Pigeon: a design visualizer for synthetic biology. ACS Synth. Biol. 2, 348–350.

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6. Chandran, D., Bergmann, F. T., and Sauro, H. M. (2009) TinkerCell: modular CAD tool for synthetic biology. J. Biol. Eng. 3, 19. 7. Clark & Parsia, L. SBOL design tool powered by semantic technologies. http:// clarkparsia.github.io/sbol/. 8. Galdzicki, M. et al. (2014) The Synthetic Biology Open Language (SBOL) provides a community standard for communicating designs in synthetic biology. Nat. Biotechnol. 32, 545–550. 9. Galdzicki, M. et al. Synthetic Biology Open Language (SBOL) Version 1.1.0 ; 2012. 10. Bartley, B., Beal, J., Clancy, K., Misirli, G., Roehner, N., Oberortner, E., Pocock, M., Bissell, M., Madsen, C., Nguyen, T., Zhang, Z., Gennari, J. H., Myers, C., Wipat, A., and Sauro, H. (2015) Synthetic Biology Open Language (SBOL) Version 2.0. 0. J. Integr. Bioinform. 12, 272. R genetic sequence data bank. 11. Bilofsky, H. S., and Christian, B. (1988) The GenBank

Nucleic Acids Res. 16, 1861–1863. 12. Ecma International, ECMA-404: The JSON Data Interchange Format. 2013. 13. Ferraiolo, J., Jun, F., and Jackson, D. Scalable Vector Graphics (SVG) 1.0 Specification; iuniverse, 2000. 14. Hart, P. E., Nilsson, N. J., and Raphael, B. (1968) A formal basis for the heuristic determination of minimum cost paths. Systems Science and Cybernetics, IEEE Transactions on 4, 100–107.

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VisBOL: Web-Based Tools for Synthetic Biology Design Visualization

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