Category Cross-Omics>Pathway Analysis/Gene Regulatory Networks/Tools and Cross-Omics>Agent-Based Modeling/Simulation/Tools

Abstract GenoCAD™ is a free web-based application to design protein expression vectors, artificial gene networks and other genetic constructs composed of multiple functional blocks called ‘genetic parts’.

By capturing design strategies in grammatical models of DNA sequences, GenoCAD guides the user through the design process. By successively clicking on icons representing structural features or actual genetic parts, complex constructs composed of dozens of ‘functional blocks’ can be designed in a matter of minutes.

GenoCAD automatically derives the ‘construct sequence’ from its comprehensive libraries of genetic parts. Upon completion of the design process, users can download the sequence for synthesis or further analysis.

Users who elect to create a personal account on the system can customize their workspace by creating their own parts libraries, adding new parts to the libraries, or reusing designs to quickly generate sets of related constructs.

In order to fully reap the potential benefits of de novo chemical ‘gene synthesis’ it has become necessary to develop tools and methodologies to streamline the design of custom DNA sequences.

Protein expression for structural studies, functional genomics, metabolic engineering, or ‘gene expression’ studies are only some of the numerous possible applications of this emerging technology. Beyond small scale ‘genetic constructs’ encompassing No more than a few interacting genes, it becomes possible to reengineer viral, bacterial, and even eukaryotic genomes.

While the number of users of this technology increases, so does the need to streamline the design of synthetic DNA sequences. GenoCAD is a web- based application filling this need by providing users with an integrated graphical development environment.

GenoCAD's design philosophy derives from the notion of genetic parts, which was first articulated to analyze ‘genomics data’.

Thinking of genetic systems as composed of parts, each with its own function and characteristics is akin to the way parts are described and used in various engineering fields. Designing complex systems through a bottom up integration of components is a dominant paradigm in engineering.

It was therefore natural that engineers approaching DNA as an engineering substrate, rather than a natural macromolecule, used the notion of biological parts as building blocks.

For instance, promoters, ribosome-binding sites (RBS), genes and terminators are all categories of parts that are needed for designing complex prokaryotic ‘genetic constructs’ such as switches and oscillators.

One could argue that systematic efforts to decompose biological sequences into functional modules that can be recombined to meet user- defined specifications is one of the most distinctive features of ‘synthetic biology’ compared to more traditional uses of recombinant DNA technologies.

GenoCAD facilitates the design of ‘artificial DNA sequences’ in three (3) ways:

1) First, GenoCAD includes a flexible system to manage libraries of public and user-defined genetic parts.

2) Second, GenoCAD relies on formal design strategies to guide both novice and experienced users in the design of structurally valid constructs for various biological applications.

3) Finally, GenoCAD's sophisticated ‘data model’ enables individual users and research groups to customize their workspace to their specific needs.

GenoCAD's Flexible Management of Genetic Parts Libraries --

By assuming that genetic designs can be synthesized, GenoCAD eliminates the need for standardizing the means by which parts are connected. It also eliminates the need to develop a collection of ‘bacterial clones’ to manage the physical implementation of the parts.

The manufacturer’s analysis also stressed the importance of basic parts used to generate new combinations of parts with specific functions. Ensuring the accuracy of the sequence and annotation of the basic parts is essential since inaccuracies at this level may affect numerous designs.

As a result of this observation, GenoCAD parts libraries are exclusively composed of ‘basic parts’ while sequences composed of multiple parts are called ‘designs’. The libraries of parts available to all GenoCAD users are limited to sequences used in peer-reviewed publications or commercial vectors. Parts are curated by a small number of experts.

Categorizing parts into functional groups has also proved challenging as the number and diversity of parts increases. It would be, for instance, questionable to record bacterial and eukaryotic promoters in the same group. Developing a more granular categorization system may lead to an exponential growth of categories that would prove cumbersome to navigate.

GenoCAD overcomes this challenge by relying on the notion of ‘grammar’. A grammar is composed of rules describing the structure of DNA sequences.

Instead of attempting to develop a universal parts categorization system, GenoCAD provides a ‘generic framework’ for the development of smaller more manageable application-specific parts-libraries. The ‘Parts’ tab of the GenoCAD user interface provides a ‘parts library browser’.

GenoCAD's Point-and-Click Design of Genetic Constructs -- In addition to providing a hierarchy of categories, grammars include sets of ‘rewriting rules’ that formalize design strategies for various types of genetic constructs. The design feature of GenoCAD embeds the grammars in a graphical user interface (GUI) that leads users through the ‘design workflow’ formalized in the grammar.

Grammars usually prompt users to begin by choosing high-level structures of their system and systematically decomposing them into individual part categories. The last step of the design process consists in selecting actual parts corresponding to specific DNA sequences.

When starting from one of the public design templates, users can quickly design constructs by simply selecting parts in a ‘parts library’ instead of going through the entire design process.

GenoCAD's Custom User Workspace --

Parts available to all users in the public parts library have been derived from peer-reviewed publications and the documentation of commercial vectors. Registered users (as stated above…) are able to create both their own parts library and their own parts.

To create a new parts library, the user selects the ‘My Libraries’ link on the ‘Design’ or ‘Parts’ tab. When the user selects the link to create a new library they are presented with a user-friendly interface to do so.

Users can also save their designs in their workspace. Designs can be saved and named at any stage of the design process. The ‘My Designs’ page provides links to delete and clone (i.e. copy) previously saved designs.

By saving a design prior to selecting parts, users can quickly clone a design template into multiple variants without having to go through the entire design process for each of them.

GenoCAD Work in Progress --

GenoCAD is a work in progress. Its sequence ‘validation tool’ makes it possible to test whether a sequence developed outside of GenoCAD is consistent with a specific grammar and parts library. This tool is still rudimentary since it simply provides pass/fail information.

Eventually, more sophisticated error messages will be generated to help user troubleshoot their sequence. As the GenoCAD user base grows, GenoCAD will support workgroups by allowing them to share parts, libraries and grammars.

The next major improvement to GenoCAD will include tools to predict the design behavior. By augmenting GenoCAD data model it is possible to compile a design DNA sequence into a Systems Biology Markup Language (SBML) file that can be simulated by one of the numerous applications that supports this standard, such as COPASI (see G6G Abstract Number 20296).

GenoCAD will then join a growing number of applications experimenting with mechanisms to derive the ‘gene network model’ encoded in genetic constructs composed of ‘standard biological parts’, such as SynBioSS and Asmparts.

GenoCAD will also integrate tools to track the synthesis and assembly of designs generated in GenoCAD. Optimizing the DNA fabrication process based on the strategies used to design a series of constructs would be extremely valuable.

System Requirements



Manufacturer Web Site GenoCAD

Price Contact manufacturer.

G6G Abstract Number 20572

G6G Manufacturer Number 104178