GeNeDA is a framework composed of open-source tools dedicated to the for the design automation of artificial gene regulatory networks based on a digital approach.
In opposition to other tools, GeNeDA is an open-source online software based on existing tools used in microelectronics and that have proven their efficiency over the last 30 years.
The complete framework can be divided in six stages and is described in the figure below
The tool requires a high-level specification provided in Verilog or in Berkeley Logic Interchange Format (BLIF) format. The Input Interface bridges the gap between those specific languages and most common ways to describe a combinatorial digital system, such as a truth table or a set of Boolean equations.
The Digital Synthesizer used to convert the input file into a set of Boolean equation is ODIN II (Peter Jamieson, Kenneth B. Kent, Farnaz Gharibian and Lesley Shannon). It provides the RTL-netlist in a standard BLIF file.
The Technology Mapper used to convert the Boolean equation into the optimal set of promoters and regulation is ABC which have been developped by the Berkeley Verification and Synthesis Research Center for Sequential Synthesis and Verification of integrated circuits in microelectronics. It provides a C-language structure giving an electronic circuit that corresponds to the best solution.
The Genetic Part Library contains all the genetic mechanisms that may be involved in a GRN. The library should be written according to a proprietary GENLIB format. Each database item involves a associated Boolean function, a continuous-time model based on rate equations and a cost. A default library including all the regulatory scheme with up to 4 regulating proteins as been designed in order to prevent the used form writting the GENLIB file. A user interface allow the user create a customized library by picking up items from this default library.
The Output Interface consists in ABC add-ons that provide output files in four formats: a BLIF file, (text file giving the name of the instantiated part as well as the regulation between parts), a graphical representation of the GRN in PNG format generated by the online design visualizer Pigeon CAD (Swapnil Bhatia) (Bhatia & Densmore 2013), a SBML model or a SystemC-AMS model.
The Simulation features are not integrated in this web interface and should be done using models provided by the output interface and third-party software
GeNeDA results from the collaboration between three laboratories:
Authors also would like to acknowledge Loïc Bauer (a last-year student of the Telecom Physique Strasbourg engineering school and the Micro-and-nanoelectronic Master of the Physics and Engineering Faculty) for his valuable contribution on the development of this tool during his MSc internship in ICube laboratory and Aurélien BROOKE (a first-year student of the Telecom Physique Strasbourg engineering school) who was in charge of the design of this website.
A paper on GeNeDA has been published in June 2016 in the Journal of Computational Biology : M. Madec, F. Pêcheux, Y. Gendrault, E. Rosati, C. Lallement and J. Haiech, "GeNeDA: An Open-Source Workflow for Design Automation of Gene Regulatory Networks Inspired from Microelectronics", Journal of Computational Biology, June 2016. doi:10.1089/cmb.2015.0229. This reference shall be used in order to cite this work.
GeNeDA has also been presented at the following conferences:
M. Madec et al., "Reuse of Microelectronics Software for Gene Regulatory Networks Design Automation", 1st international conference of the GDB BioSynSys, Paris (FR), Sept. 2016.
M. Madec et al., "EDA inspired Open-source Framework for Synthetic Biology", IEEE 2013 BioCAS Conference, Rotterdam (NL), Nov. 2013.