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Emerging Standards in Synthetic Biology

Emerging Standards in Synthetic Biology. Herbert M Sauro Michal Galdzicki and Deepak Chandran University of Washington, Seattle. SBML in a Nutshell B ottom-Up Effort. A machine-readable format for representing computational models in systems biology

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Emerging Standards in Synthetic Biology

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  1. Emerging Standards in Synthetic Biology Herbert M Sauro Michal Galdzicki and Deepak Chandran University of Washington, Seattle

  2. SBML in a NutshellBottom-Up Effort • A machine-readableformat for representing computational models in systems biology • Domain: systems of biochemical reactions • Specified using XML • Components in SBML reflect the natural conceptual constructs of the domain • Now over 200 tools use SBML Funding www.sbml.org

  3. SBML SBML Ecosystem Unambiguous Model Exchange Diagrams Databases Simulator Comparison and Compliance Semantic Annotations Journals SEDML: Simulation Experiment Description Language SBGN : Systems Biology Graphical Notation

  4. What is Synthetic Biology Synthetic Biology is the “design and construction of novel artificial biological pathways, organisms or devices, or the redesign of existing natural biological systems.” (Royal Society)

  5. 10 years of Synthetic Biology Gardner TS, et al. Construction of a genetic toggle switch in Escherichia coli. Nature 2000; 403: 339-342. Elowitzand Leibler; A Synthetic Oscillatory Network of Transcriptional Regulators Nature. 2000; 403: 335-8.

  6. Synthetic Biology Workflow “Creating cells that are able to excrete insulin at a specified rate during their optimal growth.”

  7. Overall Aim of the Standardization Effort To support the synthetic biology workflow: • Laboratory parts management • Simulation/Analysis • Design • Assembly • Repositories - preferably distributed

  8. The Immediate Need Take any current publication on a synthetic circuit and try to reproduce it, let me know how you get on.

  9. Long-term Aim of the Standardization Effort Specifically: • To allow researches to electronically exchange designs with round-tripping. • To sent designs to bio-fabrication centers for assembly. • To allow storage of designs in repositories and for publication purposes.

  10. Synthetic Biology Open Language: SBOL http://www.sbolstandard.org/ SBOL Semantic* SBOL Visual* SBOL Script First meeting in 2008, Seattle, funded by Microsoft

  11. Synthetic Biology Data Exchange Group Synthetic Biology Open Language (SBOL) http://www.sbolstandard.org/ UK, Imperial College SBOL-visual SBOL-semantic EU 7th Framework Programme iBioSim

  12. SBOL Visual (SBOLv) • Developed at the Berkeley • BIOFAB (Endy and Arkin) • Current about 40 symbols • Used to visually annotate • ‘features’ on a DNA • Three symbol groups at present: • 1. Central Dogma • 2. Genetic Engineering • 3. Devices

  13. SBOL Visual (Implemented in Spectacles and TinkerCell)

  14. Engineer SBOL: Reuse of biological parts New genetic device Create a common language for engineers to describe and send parts Synthetic Biologist A Synthetic Biology Open Language (SBOL) visual B0015 Synthetic Biologist B 81-88 89-129 1-80 Fabricate Sequence Annotation Part BioBrick Scar B0012 B0010 Terminator BioBrick Scar Terminator DNA Components semantic describe and send Michal Galdzicki

  15. type SS002 Sample cell subClassOf strain Cell UW002 MG1655 Plasmid Physical DNA type type dna pUW4510 vector insert type B0015 pSB1A2 Vector Backbone format annotation annotation annotation BBF RFC 10 subClassOf 81-88 89-129 1-80 type Part type Sequence Annotation feature feature feature Assembly Standard BioBrick Scar type type type Terminator BioBrick Scar Terminator subClassOf subClassOf subClassOf type B0012 B0010 Sequence Feature Figure 1. Diagram of the SBOL Semantic structure, illustrated with a set of information about a synthetic biology construct. a. A simplified Class (black rectangles) hierarchy (black open faced arrows) describes types (colored open faced arrows )of Individual dataelements (yellow rounded rectangles) and the composition relationships between them (closed faced arrows). The example can be read as: Sample (pink) SS002 contains UW002 cells (dark green) of the MG1655 E. coli strain, which contain a plasmid (purple) pUW4510, which is composed of an parts (dark blue) an insert B0015 and vector backbone pSB1A2. The pSB1A2 vector backbone complies with the Assembly Standard (light blue) BBF RFC 10. The B0015 sequence annotations (green) specify three features (orange), the BioBrick Scar, and the parts (blue and orange indicating multiple inheritance), B0010 and B0012, which serve as transcriptional termination signals. b. Data type Properties used to hold information for each SBOL class follow the colon.

  16. Parts Registry at MIT Database of parts, basically a wiki, object model not documented and was generally not available to the public until this year.

  17. SBOLr is a web front for a knowledge base of standard biological parts http://sbolr.bhi.washington.edu/ JBEIr Software by Timothy Ham & ZinoviiDmytriv

  18. Software support: libSBOL Repository Parts KB CAD Tool SBOL-semantic libSBOL Allow for ease of access to information by software tools, using Semantic Web standards. Sequence Editor Michal Galdzicki TinkerCell

  19. List of Software in the Working Group • Clotho (BU,Berkeley), Java Connects users to repositories of biological parts. Plugin tools then define the various functions that can be performed, mainly related to lab and parts managements. Douglas Densmore • GenoCAD (VT) Web based tool for the design of biological devices using an attribute grammar which defines the legal composition of parts. Jean Peccoud • iBioSim (Utah), JavaAdvanced simulation and analysis tool for synthetic and systems biology. Chris Myers • JBEI Repository (Java), DOE support infrastructure Timothy Ham & ZinoviiDmytriv • SBOLr (Currently Python but moving to Java)Test parts repository, ~5000 parts Michal Galdzicki • TinkerCell(UW), C++/QtExtensible visual design tool with support for modules, eg simulation, annotation. Deepak Chandran

  20. Current Status of Standard • First official release will be at Synthetic Biology 5.0 at Stanford, June, 2011 • libSBOL 1.0 available at: http://github.com • Import/Export: GenBank, RDF, JSON

  21. TinkerCell: Project to explore the potential of computer aided design in synthetic biology First prototype called Athena Developed by Bergmann and Chandranfunded by Microsoft

  22. Layered Architecture: Based on C++/Qt Octave,

  23. All Parts can be Semantically Annotated. This allow plug-ins to interpret a given design. Enzyme Enzyme catalysis Transcription Factor Reporter Translation Binding mRNA Currently there is no formal ontology for synthetic biology but one will need to be developed. Transcription Elongation Terminator Promoter Coding

  24. A TinkerCell model can be composed of sub-models

  25. A TinkerCell model can be composed of sub-models ? ? ? ? ? ?

  26. Users can add new plugins using C++, C, Octave, or Python languages

  27. Availability www.tinkercell.com (Windows, Mac and Linux, released under BSD) Contact author for details (dchandran1@gmail.com)

  28. Many C and Python packages are included with TinkerCell • Sundials • Time-course simulation • Steady state plot • structural analysis • sensitivity analysis • bifurcation analysis • parameter scan • simulation • Custom programs • Gillespie algorithm • Hill equation derivation • 2^N automatic binding events • Loops in Jacobian • lp_solve • flux balance analysis • SciPy • optimization • matrix operations • statistics • numerical methods • frequency analysis Antimony SBML and CellML support • NetworkX (lanl.gov) • graph analysis • graph layout

  29. Demo: Repressilator

  30. Acknowledgements: Collaborators and Funding • UW • Deepak Chandran, Michal Galdziki, Sean Sleight, Bryan Bartley, Alex Neilson • BioFAB (Berkeley, Stanford) • Cesar Rodriguez, Drew Endy , Chris Anderson • Virginia Tech JBEI (DOE) • Jean Peccoud Timothy Ham & ZinoviiDmytriv • Boston University CRG, Spain • Douglas DensmoreRaikGrunberg • Funding • National Library of Medicine (Galdziki) • Other funding from NIH (JSim/SBW) , NIH (SBW) and NSF (FIBR,Tinkercell), Microsoft Strategic Research, BioFAB (NSF), JBEI (DOE)

  31. Textbook:Enzyme Kinetics for Systems Biology • Available as e-book or paperback on www.analogmachine.org & • 318 pages, 94 illustrations and 75 exercises • E-book - $9.95 • Paperback - $29.95

  32. Sequence Refinement Examples include avoiding specific restriction sites or optimizing the codonusage. The sequence might also be optimized to avoid repeated regions that may be prone to recombination or secondary structures.

  33. The SBOL semantic structure annotation annotation annotation B0015 81-88 89-129 1-80 type feature feature feature type Sequence Annotation Part BioBrick Scar B0012 B0010 type type type Terminator BioBrick Scar Terminator type = instance-of

  34. Each component in the TinkerCell diagram is associated with one or more tables

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