This list was seeded by the participants of the 2008 workshop on Standards and Specifications in Synthetic Biology.
Please feel free to add information about a computation tool for synthetic biology (CADs, simulators, databases, lab managements systems, automation software, anything) to the list. Place it alphabetically, name the main project contributors, provide a canonical link to the program, and add a paragraph of descriptive text. Please date your entry.
http://antimony.sourceforge.net/ Lucian Smith, Deepak Chandran, Herbert Sauro
Antimony is a human-readable and human-writable language for describing biological modules. The modules can be connected together by declaring overlapping molecular species between two modules or via the PoPS in/PoPS out interface. The language is similar to the Jarnac language introduced by Herbert Sauro several years ago.
http://www.washington.edu/staff/deepakc/downloads/InstallAthena.exe Deepak Chandran, Frank Bergmann, Herbert Sauro
Athena is a tool for building, simulating, and analyzing genetic circuits (as well as metabolic/signaling networks, such as SBML files). It provides a visual interface for building biological modules that can be saved and later connected together. The connection can be achieved using either the PoPS interface or by defining overlapping molecular species (similar to the concept of module in CellML and SBML). In addition to simulation, Athena supports a few other useful features: Database of Ecoli regulatory network from RegulonDB, Graphical view of part sequence, Automated derivation of transcription rate equations, Interface to all Systems Biology Workbench programs, Interface with R statistical language, Easy plugin architecture
Note: Athena has been succeeded by Tinkercell
TinkerCell is a highly flexible visual tool. Although still in development, it will have all the features in Athena. In addition, TinkerCell allows a family tree of biological parts to be loaded from a database. TinkerCell comes with a drawing program that allows users to draw their own graphical representations (if they do not like the defaults). C libraries, such as simulations or graph analysis, can easily be incorporated into TinkerCell. New plug-ins can also be added very easily.
http://web.mit.edu/jagoler/www/biojade/ Jonathan Goler
BioJADE is a design and simulation tool for synthetic biological systems. BioJADE is written in Java, and makes interactive use of BioBrick Repositories. BioJADE enables system designers to specify a system abstractly, tune it, simulate its behavior using a variety of simulators, and finally package the part for use by either the designer or the public.
http://igem.uwaterloo.ca/BioMortar Andre Masella
BioMortar is a lab management system designed specifically to deal with BioBricks. It is also capable of generating cookie-cutter protocols from user-specified templates and tracking the results, including gel images. It is released under the MIT License.
Sarah Richardson, Joel Bader, Jef Boeke
BioStudio is both an integrated development environment and a genome version control system, with the ability to modify nucleotide sequences automatically or manually at multiple resolutions. It uses Gbrowse from the GMOD project for its user interface and is currently able to locate and manipulate potential and existing restriction enzyme recognition sites, identify and incorporate unique sequences for PCR identification of wildtype and synthetic sequence, edit existing genome features, and incorporate and annotate user-created genome features. Each version of the genome is encoded in a Gene Feature Format (GFF) file, which is then displayed by the open source annotation viewer GBrowse and stored in a branching version control system. Collaboration and transparency is accomplished through the use of a wiki. Each feature in a GFF file will have a corresponding article in the wiki, where registered users can actively discuss its treatment. To ensure that BioStudio actually meets the needs of synthetic biologists, it is under development alongside the design of a synthetic Saccharomyces cerevisiae genome, SC2.0.
http://brickit.wiki.sourceforge.net/ Raik Gruenberg and you?
BrickIt aims to create a portable web-based registry that helps synthetic biologists to plan, organize and track their local biobrick samples. The database-backed web server can be downloaded as virtual machine to quickly set up a local registry which coordinates the work within a lab, institute or community. Although the data remain local, the web server itself is an open-source project and new functions or improvements can be easily exchanged between the different local registries. BrickIt thus also offers a platform for the shared development of tools and infrastructure that foster the collaboration within the Synthetic Biology community. BrickIt and everything it relies on are open source and free. BrickIt itself is licensed under the GPL.
http://www.clothocad.org Douglas Densmore, J. Christopher Anderson, Alberto Sangiovanni-Vincentelli
Clotho presents a design environment to manipulate DNA sequence information and store the manipulated data as packaged "parts" back to part repositories. It provides a robust sequence editing environment (highlighting, restriction enzyme library, basic DNA analysis features), a parts management system (database browsing, search, and manipulation), and an algorithm manager which allows the introduction of user developed algorithms (currently includes assembly algorithms). The tool is very much in the early stages of development but an alpha release is available. Clotho is part of a larger development of platform-based design tools for synthetic biology. The tool is open source under a BSD license.
http://moleculamaxima.com/ Molecula Maxima
DilutionMagic is a clever dilution calculator which can calculate your serial dilution steps. It can do it for arbitrary concentrations values and arbitrary volumes.
http://www.genedesign.org Sarah Richardson, Joel Bader, Jef Boeke
GeneDesign is a suite of algorithms that allow users to edit several features of protein coding sequences, including codon usage and restriction enzyme recognition site presence. It will then generate a list of oligos and a road map for the assembly of the sequence by PCR It is written in Perl and is served over the internet; the code is available for local installations. A new, improved version is due before the end of 2008. PMID: 16481661
This integrated, stand-alone secure software helps you create DNA constructs on your desktop with unprecedented ease and speed. Available for Mac and PC. For details see Villalobos et al.
http://soft.synth-bio.org/genetdes.html Guillermo Rodrigo, Javier Carrera, Alfonso Jaramillo
GeNetDes is a tool to design transcriptional networks with targeted behavior that could be used to better understand the design principles of genetic circuits. It is a Simulated Annealing optimization algorithm that explores throughout the space of transcription networks to obtain a specific behavior. The software outputs a transcriptional network with all the corresponding kinetic parameters in SBML format. Our tool can also be applied to design networks with multiple external input and output genes. The software, a tutorial manual, parameter sets and examples are freely available in our website. We are currently extending Genetdes to design networks by assembling standardized biological part models. The models contain data obtained from part characterizations. We will evolve such circuits by replacing model parts to reach the imposed design specifications. In addition, we will incorporate the effect of the chassis by including the interaction with the cellular resources.
http://www.genocad.org Yizhi Cai, Michael Czar, Julie Marchand, Jean Peccoud
GenoCAD is a web-based application guiding users through the design of part-based genetic systems. GenoCAD uses context-free grammars to formalize design strategies for synthetic genetic systems. This approach provides a path to organizing libraries of genetic parts according to their biological functions. It also provides a framework for the systematic design of new genetic constructs consistent with the design principles expressed in the grammar. Using parsing algorithms, GenoCAD enables the verification of existing constructs.doi:10.1093/bioinformatics/btm446
Genome Compiler is an intuitive all-in-one software platform for life scientists in the genetic engineering, molecular biology and synthetic biology fields, and provides a comprehensive tool for:
- DNA design and visualization
- Data management
- Collaboration platform
- Seamless DNA ordering
Genome Compiler is free for academia users and is available online and in a downloadable version so you can easily access your data on Genome Compiler from anywhere you are. The software supports Windows and Mac. In addition, the software supports common file formats such as: FASTA, Vector NTI, SnapGene, Geneious, Clone Manager, Serial Cloner, Plasma DNA, ApE, DNAStar, etc.
http://osslab.lifesci.warwick.ac.uk/Tinker.aspx Kent McClymont, Orkun S Soyer
TINKER is a metabolic pathway design/search tool. It compiles the entire set of known reactions and compounds from the latest version of the Rhea database and converts this data into a directed graph. Nodes and edges on this graph correspond to metabolites and reactions, respectively, and thus the entire graph corresponds to the current known metabolic universe. Within this graph, TINKER searches for thermodynamically feasible paths between user defined "source" and "target" compounds and returns the found paths as metabolic pathways (rank-ordered by thermodynamic feasibility)
http://salislab.net/software Daniel Cetnar, Tian Tian, Iman Farasat, and Howard M. Salis
The Operon Calculator combines 15 biophysical models and design rules to automatically design synthetic operon sequences for maximum tunable control over RNA and protein expression levels. The algorithm also eliminates the presence of several overlapping, undesired genetic elements that will inevitably break the operon's function.
http://www.mpi-magdeburg.mpg.de/projects/promot/ Katrin Kolczyk, Sebastian Mirschel, Michael Rempel, Mario A. Marchisio
ProMoT is the process modeling tool designed for the convenient setup of synthetic biology models in a modular fashion. Genetic circuits are built just by placing biological parts on a canvas (using drag and drop) and by connecting them through ”wires” that enable ﬂow of signal carriers, as it happens in electrical engineering. ProMoT supports two different modeling approaches -- a quantitative and a qualitative modeling approach. The quantitative approach is based on differential algebraic equations (DAEs) whereas the qualitative approach is a description of the system in the form of logical equations. The final code associated with a circuit can be exported into Matlab or SBML format (Level-1 and Level-2) allowing to run both deterministic and stochastic simulation.
For more detailed information, please refer to the recent papers ProMoT: Modular Modeling for Systems Biology and Computational design of synthetic gene circuits with composable parts or the synthetic biology research page Synthetic Biology at ETH Zurich.
Ribosome Binding Site (RBS) Calculator
http://salislab.net/software Howard Salis, Ethan Mirsky, and Christopher Voigt, Nature Biotechnology, v27, 2009
The Ribosome Binding Site (RBS) Calculator is an engineering design method that predicts the translation initiation rate of a protein coding sequence in bacteria. You can use the RBS Calculator to generate synthetic ribosome binding site sequences and to rationally control the production rate of any protein in bacteria from 0.1 to 100,000+ on a proportional scale.
The RBS Calculator is used by GenScript to synthesize DNA sequences with custom-designed ribosome binding sites.
The RBS Calculator is embedded into Genome Compiler, an intuitive all-in-one software platform for DNA design, which is free for academics to use.
Relevant papers: Translation Rate is Controlled by Coupled Trade-offs between Site Accessibility, Selective RNA unfolding and Sliding at Upstream Standby Sites
A Predictive Biophysical Model of Translational Coupling to Coordinate and Control Protein Expression in Bacterial Operons
Automated Design of Synthetic Ribosome Binding Sites to Control Protein Expression
http://salislab.net/software Breakthrough Article: Espah Borujeni A., D.M. Mishler, J. Wang, W. Huso, and H.M. Salis. Nucleic Acids Research. v44(1). 2016
Riboswitches are shape-changing regulatory RNAs that bind chemicals and regulate gene expression, directly coupling sensing to cellular actuation. The Riboswitch Calculator designs synthetic translation-regulating riboswitches that bind to specific chemicals and activate gene expression. Starting with a known RNA aptamer, the algorithm automatically optimizes the (up to) 30 nucleotide sequences that appear before and after the RNA aptamer to maximize the activation of gene expression. The algorithm combines a statistical thermodynamic model of translation with genetic algorithm optimization. The algorithm's predictions were validated by constructing and characterizing 62 synthetic riboswitches that utilized six different RNA aptamers to sense a diverse range of chemicals (theophylline, tetramethylrosamine, fluoride, dopamine, thyroxine, 2,4-dinitrotoluene). The riboswitches' activation ratios were the highest reported to-date for their respective RNA aptamers.
Relevant paper: Automated Physics-based Design of Synthetic Riboswitches from Diverse RNA Aptamers
RBS Library Calculator
Iman Farasat, Manish Kushwaha, Jason Collens, Michael Easterbrook, Matthew Guido, and Howard Salis, Molecular Systems Biology, v10(6). 2014
The RBS Library Calculator designs the smallest RBS library sequence that uniformly searches a desired translation rate space, enabling one to efficiently identify optimal protein expression levels in plasmid- or chromosomally-encoded genetic systems. The algorithm has three modes. Search mode allows one to explore the largest possible translation rate space, across a 100,000-fold proportional scale, using the smallest RBS library (16 to 32 variants). Zoom mode allows one to design a minimal RBS library to search a targeted translation rate space between a minimum and maximum. Genome Editing mode designs genomic RBS libraries with a minimal number of consecutive mutations, suitable for designing the mutagenic oligonucleotides needed for MAGE genome mutagenesis. The method has been used to efficiently tune genetic circuits and optimize metabolic pathways.
Relevant paper: Efficient Search, Mapping, and Optimization of Multi-protein Genetic Systems in Diverse Bacteria
http://iasi.bu.edu/~batt/rovergene/rovergene.htm Gregory Batt, Calin Belta
RoVerGeNe is a software tool for the analysis of dynamical properties of gene networks. Unlike conventional ODE numerical simulation tools, it allows
- to test whether a dynamical property holds for ranges of parameters
- and to find parameter sets for which a given dynamical property hold
The tool is thus useful for robustness analysis and tuning of gene networks. See Bioinformatics paper.
SBW (Systems Biology Workbench)
http://simthyr.sf.net Johannes W. Dietrich
SimThyr is a continuous numeric simulation program for thyroid homeostasis. It is based on a parametrically isomorphic model of the overall system. Applications of this program cover research, including development of hypotheses, and education of students in biology and medicine, nurses and patients.
- Dietrich JW, Landgrafe G, Fotiadou EH. TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. J Thyroid Res. 2012;2012:351864. doi: 10.1155/2012/351864. Epub 2012 Dec 30. PMID 23365787; PMCID PMC3544290.
- Dietrich JW, Landgrafe-Mende G, Wiora E, Chatzitomaris A, Klein HH., Midgley JE, Hoermann R. Calculated parameters of thyroid homeostasis: Emerging tools for differential diagnosis and clinical research. Frontiers in Endocrinology. 2016; 7:00057. doi: 10.3389/fendo.2016.00057.
Citation: Dietrich JW (1994-2016) SimThyr 4.0. Fairfax, VA: sourceforge, http://simthyr.sf.net. RRID:SCR_014351.
http://synbioss.sourceforge.net/ Yiannis Kaznessis, Tony Hill, Vassilis Sotiropoulos, Jonathan Tomshine
SynBioSS (Synthetic Biology Software Suite) is a software suite for the quantitative simulation of biochemical networks using hybrid stochastic algorithms. We believe that one shouldn’t need to know how to program (or use command-line) to use sophisticated numerical methods. Through this software, we intend to put the most powerful techniques for simulating chemically reacting networks into the hands of biologists (or any scientist who can put them to good scientific use). SynBioSS can accurately simulate any system modeled as a network of reactions. In order to achieve this result, we wrapped up state-of-the-art algorithms inside a user friendly graphical interface (GUI) that handles input data, runs the simulations and vividly visualizes simulation results, without requiring any programming background from the user. The software is open and runs on any of the three platforms most used by scientists: Windows, Macintosh, and Linux.
http://synbiotools.org Swapnil Bhatia (Boston University)
Synbiotools hosts a free and growing software suite for engineering biology including tools for visualization, combinatorial genetic design generation, circuit design, and build automation.
Engineering platform for building and testing cellular circuits (Deepak Chandran, UW, Seattle)
TinkerCell is an extensible platform for editing and simulating cellular networks. Users can operate the software at different levels including graphical point and click or via an interactive console. While the main interface is visual, programmers may add new features by writing custom programs in C or Python. TinkerCell is designed to incorporate information from database(s), thus the models store information such as rate constants, gene sequences and promoter strengths. Networks can be "modularized" and connected to one another. TinkerCell is cross platform and written in C++. A Python console is provided for interactive control.
http://tinyseq.com Jason Morrison, Mackenzie Cowell
TinySeq is the minimal minimal part storage tool. It assigns a unique url to a given sequence, and stores the sequence's construction format & plasmid. TinySeq supports part composition via the url, so you can get the assembled sequence of two parts simply by asking for something like tinyseq.com/mlc:1+mlc:2. We built tinyseq to reveal what other features besides assigning an accession number (mlc:1) to a sequence would be useful for users at a lab bench who are looking for tools to help them keep their assemblies in order.
http://www.cellml.org/tools/pcenv/ Andrew Miller, Justin Marsh, Alan Garny
PCEnv is an environment for creating and simulating arbitrary mathematical models, including mathematical models in the fields of systems and synthetic biology. PCEnv uses CellML as a native format for storing models.
http://soft.synth-bio.org/protdes.html Maria Suarez, Pablo Tortosa, Alfonso Jaramillo
Synthetic Biology will benefit from future efforts using first-principles to design biological macromolecules. Ideally, this would mean using the same software and parameters to fold a protein than to design a protein with a given fold (inverse folding problem). Recent work has demonstrated that it is possible to experimentally validate such approaches, by using appropriate physical modelling. We have developed a tool able to incorporate such successful procedures by using a leading molecular dynamics software. Our tool PROTDES is an open-source toolbox for computational protein design using the CHARMM package. This allows the integration of molecular dynamics within the protein design, allowing to extend the physical description more than it has been possible with current software. The procedure automatically finds the suitable mutations optimizing a protein folding free energy. It mutates residue positions to find the best amino acids in an arbitrary protein structure without requiring pairwise approximations. It implements an heuristic optimization algorithm that iteratively searches the best amino acids and their conformations for a an arbitrary set of positions within a structure. The users will be able to create their own procedures for protein design using their own physical protocol, which we exemplify by already incorporating three alternative effective energy functions.Our versatile software will allow synthetic biologists using physical models to use a standard molecular dynamics software for protein design.
http://j5.jbei.org Nathan J. Hillson
Recent advances in Synthetic Biology have yielded standardized and automatable DNA assembly protocols that enable a broad range of biotechnological research and development. Unfortunately, the experimental design required for modern scar-less multipart DNA assembly methods is frequently laborious, time-consuming, and error-prone. A web-based software tool, j5, automates the design of scar-less multipart DNA assembly protocols including SLIC, Gibson, CPEC, and Golden Gate. The key innovations of the j5 design process include cost optimization, leveraging DNA synthesis when cost-effective to do so, the enforcement of design specification rules, hierarchical assembly strategies to mitigate likely assembly errors, and the instruction of manual or automated construction of scar-less combinatorial DNA libraries. j5 can be used to build combinatorial libraries and applied to the preparation of linear gene deletion cassettes. These innovations save researchers time and effort, reduce the frequency of user design errors and off-target assembly products, decrease research costs, and enable scar-less multipart and combinatorial DNA construction at scales unfeasible without computer-aided design. The j5 software has been exclusively licensed to TeselaGen Biotechnologies for commercial use and distribution.
http://j5.jbei.org Joanna Chen, Douglas Densmore, Timothy Ham, Zinovii Dmytriv
A web-based bioCAD software tool, DeviceEditor, provides a graphical design environment that mimics the intuitive visual whiteboard design process practiced in biological laboratories. The key innovations of DeviceEditor include visual combinatorial library design, direct integration with scar-less multi-part DNA assembly design automation, and a graphical user interface for the creation and modification of design specification rules. DeviceEditor liberates researchers from DNA base-pair manipulation, and enables users to create successful prototypes using standardized, functional, and visual abstractions. Open and documented software interfaces support further integration of DeviceEditor with other bioCAD tools and software platforms. DeviceEditor saves researcher time and institutional resources through correct-by-construction design, the automation of tedious tasks, design reuse, and the minimization of DNA assembly costs. The DeviceEditor software has been exclusively licensed to TeselaGen Biotechnologies for commercial use and distribution.
https://public-registry.jbei.org/static/vesa/VectorEditor.html Zinovii Dmytriv, Timothy Ham, Hector Plahar, Joanna Chen
Open source, web based cross platform and cross browser DNA sequence editing and analysis tool.
http://igem.synbioreview.com/ Michal Galdzicki
A reference collection of iGEM software projects 2007-2011. This is a compilation of all the software projects large and small created throughout the iGEM competition. On this site you can find the description of the computational tool, a link to the project page and source code.