Team:Stanford/sBOLvPage

Synthetic Biology Open language Visual: SBOL-V

Synthetic Biology Open Language Visual (SBOLv) is a graphical notation that supports biological device development. It provides a formal notation for describing the physical composition of basic parts into composite parts during the development of biological devices. It is targeted for use by biological engineers in forward engineering projects. It encourages and supports model-driven engineering.

SBOLv is an open standard that balances the benefits of top-down control with the bottom-up needs to communicate. The notation is flourishing in an environment of open communication while rigorously defining symbols, syntax, and grammar. SBOLv is an abstract tool for solving concrete problems. It has a rigorous and consistent structure and is being used in concrete software tools while working on concrete Synthetic Biology projects.

SBOLv is a component of the Synthetic Biology Open Language (SBOL), an emerging open standard for structuring and exchanging information between members of the Synthetic Biology Community. SBOL has four components; a relational model (Core Data Model), a semantic model (SBOL Semantic), a scripting language (SBOL Script), and a graphical notation (SBOL Visual). SBOL promises to offer biological engineers with a comprehensive set of standards and tools in support of data exchange and communication.

Central Dogma Symbols

Part	Forward	Reverse	Other	Information
Origin of Replication				The circle represents a plasmid. The rectangle signifies the site of the replication origin on the plasmid. An indication of the plasmid copy number is OPTIONAL but MUST be located in the center of the circle. Molecules per cell is the RECOMMENDED scale. Secondly, the shorthand version of the Origin of Replication, Annotated. The rectangle is omitted. This symbol SHOULD be used for rapid drawing and communication. However, the Origin of Replication, Annotated symbol is RECOMMENDED.
Constitutive Promoter				Constitutive Promoter: Represents a DNA sequence that promotes RNA polymerase binding and transcription in the forward direction. The open square indicates constitutive transcription. The arrow and its presence on the DNA strand indicates directionality.
Inducible Promoter				Represents a forward promoter that is induced. The "+" sign indicates that promoter needs to be induced to initiate transcription.
Repressible Promoter				Represents a forward promoter that can be repressed to block transcription. The "-" sign suggests the promoter's repressibility and the rightward arrow, as in the case of the rightward constiutive promoter, indicates directionality.
Promoters With Operators				A combination of two symbols, one indicates a forward promoter. The open boxes on either or both sides of the promoter indicate an upstream or downstream operator. The box can be filled with information about the specific location and functionality of the operator.
Open Reading Frame				Represent an rightward-facing ORF. The tag shape emphasizes the single continuous DNA fragment of the ORF and then arrowhead at the end of the tag represents the 5' to 3' directionality of the reading frame.
Translational Start Site				Represents a Shine-Delgarno sequence in the rightward strand of prokaryotes, IRES in viruses and ribosome loading structure in eukaryotes. The half-circle is intended to visually represent the ribosome binding to a DNA strand.
Terminator				Represents the location on the gene where transcription ends. The "T" shape not only reminds one visually of a "T" for "Terminator," but also the t-structure visually represents a hairpin structure that is formed at the end of transcription.
Primer Site				Represents the location where the primer binds in order for transcription to occur.
Ribonuclease Site				Represents the site where RNA is cut. In this icon and the following, a dashed line corresponds to functional elements encoded on RNA. The "x" is supposed to correlate to the "cutting" of the RNA.
RNA Stability Elements				Corresponds to the stability of the RNA linked to secondary structure at this point. Once again, the dashed line signifies an RNA-encoded function. In this image and the following, the size of the circle is representative (on a log-based scale) of the half life of the RNA, aka its "stability." The larger circle appearing here signifies a stable molecue, with decreasing size corresponding to decreasing stability.
Protease Site				Represents the site where proteins are broken down or "cut." The image is intentionally similar to the ribonuclease site, only the solid line here and in the following images corresponds to proteins.
Protein Degradation Elements				This image corresponds to the stability of the protein. Once again, the solid line signifies protein. In this image and the following, the size of the circle is representative (on a log-based scale) of the protein halflife protein, aka its "stability." The larger circle appearing here signifies a more stable form.

Genetic Engineering Symbols

Part	Forward	Reverse	Other	Information
Barcode				Provides additional information about a gene (e.g., its name, date of synthesis and/or the individual or team that synthesized it). The "x__ " is meant to remind someone of a place on a document where one can put their signature and sign off. Similarly, here is a location where one can provide their "signature."
Prefix				Represents a quick visual of the location of the engineered prefix sequence as recommended by the BioBricks Registry. The half circle will be clear and easy to pick up as a location of genetic engineering, and it elegantly combines with a smaller circle representing the "suffix" to form the scar.
Suffix				Represents a quick visual of the location of the engineered suffix as recemmended by the BioBricks Registry. The circle, once again, will be clearly noticed as a location of genetic engineering and fits elegantly with the prefix symbol.
Scar				Represents the location where two engineered parts have been joined- specifically where the prefix and suffix have joined.
Restriction Sites				A restriction endonuclease site that results in 3', 5' or blunt overhangs. The diagonal line is meant to illustrate the geometry of the cut site and the sticky ends.
Type IIs Off-Set Cutters				A restriction endonuclease site that binds at one location on the DNA strand, but cuts at a location downstream from this initial site. It results in an overhang.

Documents

The formal RFC Document is entitled BBF RFC. 16: Synthetic Biology Open Language Visual (SBOLv) Specification.

Acknowledgements

It takes many individuals to nurture the birth of a new language. We are indebted to our colleagues; Drew Endy, Cesar Rodriguez, Jerome Bonnet, Barry Canton, Deepak Chandran, Douglas Densmore, Lesia Bilitchenko, Joanna Chen, Tim Ham, Raik Gruenberg, Jason Kelly, Adam Liu, Richard Mar, Lance Martin, Alec Nielsen, Robert Ovadia, Randy Rettberg, Herbert Sauro, Reshma Shetty, Francois St-Pierre, Emma Weeding, and Ming Yan. Thank you for your support and advice.

We would also like to extend our thanks to the Berkeley Software iGEM team for 2009, whom we collaborated with in our designs and who will be using parts of the language in their software tools, available through their wiki, which facilitate in the design of biological parts.

References

Novere, et al. Systems Biology Graphical Notation. Nature Biotechnology 2009 vol. 27 (8) pp. 735-41

Matsuoka, et al. Consistent design schematics for biological systems: standardization of representation in biological engineering. Journal of the Royal Society Interface. EPub June 3 2009

Shetty, et al. Engineering BioBrick vectors from BioBrick parts. Journal of Biological Engineering. 2008; 2: 5.

Voigt. Genetic parts to program bacteria. Current Opinion in Biotechnology, 17(5):548–57, Oct 2006.

Andrianantoandro, et al. Synthetic biology: new engineering rules for an emerging discipline. Molecular Systems Biology. 2006 vol. 2 pp. 2006.0028.

Endy. Foundations for engineering biology. 2005 vol. 438 (7067) pp. 449-53.