Table 1.
A comprehensive list of software tools available for solving bio-design automation tasks
| Realm | Tool name | Description |
|---|---|---|
| Specification | Eugene (Oberortner and Densmore 2014) | A rule-based specification language, which is able to incorporate abstraction layers and automatically generate combinatorial biological devices from components (eugenecad.org) |
| Pigeon (Bhatia and Densmore 2013) | Translates textual representations of nucleic acids into standardized visual representations (pigeoncad.org) | |
| GEC (Pedersen and Phillips 2009) | A language for modular specification of proteins and genes and their interactions; such specifications can then be compiled into standard biological sequences (biology.azurewebsites.net/gec) | |
| Phoenix | A tool that guides users through an automated, iterative design–build–test–learn cycle; with an ability to learn from empirical data, it can complete the closed-loop automation | |
| Proto/Biocompiler (Beal et al. 2011) | Generates optimized genetic regulatory network designs from specifications written in a high-level programming language (synbiotools.bbn.com) | |
| GSL (Wilson et al. 2016) | A language that facilitates design of large and complex DNA constructs used to engineer genomes; it also incorporates a set of low-level DNA manipulation primitives | |
| Kera (Dhar 2010) | An object-oriented programming language for synthetic biology, which is tempered by the biopart rule library, Samhita; Kera captures the knowledge regarding the interaction of genome components and catalytic molecules | |
| Antimony (Smith et al. 2009) | Text-based modular human-readable/writable model definition language with capabilities of easy translation into SBML | |
| ProMot (Mirschel et al. 2009) | A tool for construction and manipulation of biological dynamic models based on differential-algebraic equations ProMot is matched with the simulation environment Diana (www2.mpi-magdeburg.mpg.de/projects/promot) | |
| Molecula Maxima | Contains a programming IDE called Cytostudio for a synthetic biology programming language called Synthetic; Synthetic is a bio-hardware description language (moleculamaxima.com) | |
| MoSeC (Misirli et al. 2011) | Java application capable of generating DNA sequences. MoSeC has the ability to generate FASTA, GenBank, EMBL, and SBOL formats from SBML and CellML models (ico2s.org/software/mosec.html) | |
| Asmparts (Rodrigo et al. 2007) | A deprecated tool for modular specification of biological devices; Asmparts takes advantage of standardization by considering a model for each part in the design | |
| Design | Cello (Nielsen et al. 2016) | Compiles Verilog code specifying a logic circuit to a DNA sequence, with prediction of the design correctness; outputs are Eugene and SBOL compatible (cellocad.org) |
| Merlin (Quintin et al. 2016) | Genomic reprogramming tool exploiting Multiplex Automated Genome Engineering (MAGE), resulting in simultaneous multiregion genome modification (merlincad.org) | |
| Double Dutch (Roehner et al. 2016a ) | Web application for designing libraries of biosynthetic pathway variants based on design of experiments (DOE) matrices (clothocad.org/doubleDutch) | |
| RBS Calculator (Salis et al. 2009; Borujeni et al. 2013) | Allows for predicting and controlling translation initiation and protein expression in bacteria; can also be used for optimizing synthetic RBS sequences to achieve a targeted translation initiation rate (denovodna.com/software) | |
| GenoCAD (Czar et al. 2009) | A gene design and simulation tool with its own repository of biological parts; it incorporates various grammars/libraries and supports GenBank format (genocad.com) | |
| TeselaGen | A cloud-based SBOL compliant solution for sequence editing, combinatorial gene design, and assembly automation (teselagen.com) | |
| BioJADE (Goler 2004) | A java-based design and simulation tool for synthetic biological systems with interactive use of BioBrick repositories (web.mit.edu/jagoler/www/biojade) | |
| DeviceEditor | Maps the DNA sequence and feature annotations underlying each part to a graphic icon; icons can then be drag-and-dropped about a visual design canvas (j5.jbei.org/bin/deviceeditor.pl) | |
| SBROME (Huynh et al. 2013) | Given genetic circuit topology and dynamics, designs circuit with parts that minimize cross talk and incompatibility (tagkopouloslab.ucdavis.edu/software.html) | |
| Salis Lab calculators (Borujeni and Salis 2016) | A number of mathematical tools for synthetic biology design process (salislab.net/software) | |
| DeskGen | A genome-editing platform that combines the use of a CRISPR/Cas9 tool with the convenience of a genome browser (deskgen.com) | |
| Genome Compiler | A software platform incorporating advanced design tools, a variety of plasmids and parts repositories, direct connections to an array of DNA synthesis providers and laboratory automation services (genomecompiler.com) | |
| MatchMaker (Yaman et al. 2012) | Automates three steps: feature matching for regulatory relationship satisfaction, signal matching for expression level compatibility, and part matching to find physical DNA sequence in a database | |
| Mfold (Zuker 2003) | Analysis of DNA/RNA folding as well as free energy determination and structure display (unafold.rna.albany.edu) | |
| Rosetta (Leaver-Fay et al. 2011) | Computes the expected structure of natural proteins and design of new proteins (boinc.bakerlab.org/rosetta) | |
| GLAMM (Bates et al. 2011) | Provides maps for metabolic pathways, biosynthesis of secondary metabolites, and macrobial metabolism (glamm.lbl.gov) | |
| OptCircuit (Dasika and Maranas 2008) | An optimization-based framework that automatically identifies the circuit components from a list and connectivity that brings about the desired functionality. | |
| AutoBioCAD (Rodrigo and Jaramillo 2013) | Fully automated computational design of regulatory circuits in Escherichia coli; is able to compile the design into a nucleotide sequence | |
| Parts & Pools (Marchisio 2014) | A framework for modular design of bacterial synthetic genetic circuits from standard biological parts and pools of molecules as signal carriers | |
| Build/assembly | Puppeteer (Vasilev et al. 2011) | Liquid-handling automation tool capable of handling various protocols and laboratory resources; output is Common Human Robot Instruction Set (CHRIS); a compiler then translates CHRIS into a human/machine executable language |
| Raven (Appleton et al. 2014a) | DNA assembly planning tool for high throughput cloning; supports modern assembly methods such as BioBrick, MoClo, and Gibson Assembly; can output computer-readable or human-readable assembly instructions for liquid-handling automation (ravencad.org) | |
| DNALD (Blakes et al. 2014) | DNA assembly planning tool for binary assembly; improves on algorithm performance of prior binary algorithms (dnald.org/planner/index.html) | |
| Fluigi (Huang and Densmore 2014) | Automates the design of microfluidic devices used in synthetic biology by optimizing their layout; specifications are in the text-based MINT language | |
| 3DuF | Visual CAD tool for the design of microfluidic devices; outputs STL for CNC milling and SVG for lithography, as well as a textual JSON representation (cidarlab.github.io/3DuF) | |
| j5 (Hillson et al. 2011) | Web-based DNA assembly automation tool with ability to design assemblies and oligonucleotides for SLIC/Gibson/CPEC/SLiCE and Golden Gate; also performs cost analysis for choices of full synthesis, PCR/SOE, or oligo embedding (j5.jbei.org/bin/j5_entry_form.pl) | |
| PR-PR (Linshiz et al. 2014) | A cross-platform high-level biologist-friendly standard language used for management of liquid-handling robotics and microfluidic automated platforms. | |
| Aquarium | An assembly design tool for generating scalable, reproducible, and transferable molecular biology workflows (aquarium.bio) | |
| Primer3 (Koressaar and Remm 2007; Untergasser et al. 2012) | A tool used to design and analyze primers for PCR reactions with the ability to select primers for sequencing reactions and hybridization probes (bioinfo.ut.ee/primer3) | |
| Test/analysis | TASBE tools | A variety of synthetic biology automation software tool for tasks from high-level specification to part assignment and assembly (synthetic-biology.bbn.com/tasbe.html) |
| Bioconductor (Huber et al. 2015) | Analysis and comprehension tool that uses the open-source statistical language, R; AMI and Docker images are available (bioconductor.org) | |
| FlowCal (Castillo-Hair et al. 2016) | A library for reading, analyzing, and calibrating flow cytometry data; it accepts FCS files as input and is compatible with different calibration particles, fluorescent probes, and cell types | |
| FlowJo | A software application with an integrated environment for viewing and analyzing flow cytometry data; the user interface (UI) is presented as the workspace of experimental data, statistics, gates, as well as tabular and graphical layouts (flowjo.com) | |
| Data | ICE (Ham et al. 2012) | A registry platform for robust data storage for DNA components, integrated tools for part characterization, and secure access and information sharing (public-registry.jbei.org) |
| SBOL Stack (Madsen et al. 2016) | An RDF-based repository of SBOL represented synthetic biology parts and devices with an ability to execute search queries (sbolstack.org) | |
| GenBank (Bilofsky and Christian 1988) | A genetic sequence database containing a complete repository of public DNA sequences with corresponding annotations; GenBank also has a widely used file format for representing such sequences (ncbi.nlm.nih.gov/genbank) | |
| Registry of Standard Biological Parts | The iGEM repository including parts that are used in BioBrick assembly; this repository has more than 20,000 documented parts (parts.igem.org) | |
| Clotho (Densmore et al. 2009) | A database for storing synthetic biological parts data as well as a framework for applications to engineer them (clothocad.org) | |
| Owl (Appleton et al. 2014b) | A tool for creating datasheets for biological entities with an ability to perform data analytics services (cidar.bu.edu/owl) | |
| Phagebook | A Clotho 3.0 app that serves as a social network that also integrates laboratory inventory management; publication announcements are also supported | |
| Viz-a-Brick | A search and navigation tool for the iGEM registry of standard biological parts with quick and easy access to global and local relationships between parts in the registry (gcat.davidson.edu/vizabrick) | |
| BioModels database (Chelliah et al. 2013) | A reference repository hosting mathematical models that describe the dynamic interactions of biological components at various scales; most model components are cross-linked with external resources to facilitate interoperability (ebi.ac.uk/biomodels-main) | |
| Simulation | iBioSim (Myers et al. 2009) | A simulation and design tool focused on genetic circuits specified in SBML or SBOL format; has the ability to analyze metabolic networks and cell-signaling pathways, as well as modeling and visualization of multicellular and spatial models (async.ece.utah.edu/iBioSim) |
| COPASI (Hoops et al. 2006) | Simulation and analysis tool for biochemical networks and their dynamics; accepts models in SBML format and analyzes them using ODE as well as stochastic algorithms (copasi.org) | |
| SynBioSS (Hill et al. 2008) | A suite of software for the modeling and simulation of synthetic genetic constructs; it uses the registry of standard biological parts, a database of kinetic parameters, and both graphical and command-line interfaces to multiscale simulation algorithms (synbioss.sourceforge.net) | |
| TinkerCell (Chandran et al. 2009) | Incorporates a diagram that is detailed enough so that it can be mapped to models or experimental results; various mathematical analyses can then be run on those models (tinkercell.com) | |
| Gro (Jang et al. 2012) | A language for programming, modeling, specifying, and simulating the behavior of cells in growing microcolonies of microorganisms; Gro can simulate cell growth, division, intrinsic and extrinsic noise, as well as diffusing molecular signals (depts.washington.edu/soslab/gro) | |
| Morpheus (Starruß et al. 2014) | A modeling environment for simulating cell-based models with ordinary differential equations and reaction–diffusion systems; multiscale biological models can be defined in biological terms and mathematical expressions—it supports model construction, simulation, visualization, and batch processing (imc.zih.tu-dresden.de/wiki/morpheus/doku.php) | |
| PySCeS (Olivier et al. 2004) | Provides a variety of tools for the analysis of cellular systems; these include a human readable model description language, a structural, and a bifurcation analysis module—PySCeS supports SBML and SED-ML (pysces.sourceforge.net) | |
| CellDesigner (Funahashi et al. 2008) | A structured diagram editor for drawing gene-regulatory and biochemical networks, with integrated SBML ODE solver, SBML simulation core, and COPASI (celldesigner.org) | |
| Jarnac (Sauro 2000) | A Systems Biology Workbench (SBW) reaction simulator that includes both deterministic and stochastic time course simulation, steady-state analysis, basic structural properties of networks, and more (sbw.kgi.edu/software/jarnac.htm) | |
| JDesigner | An SBW network design tool with ability to export SBML file format; JDesigner is capable of connecting to Jarnac to perform simulation tasks (sbw.kgi.edu/software/jdesigner.htm) | |
| Mathematica | Incorporates an exclusive solution for synthetic biology; it is capable of performing the complete workflow from data import to analysis | |
| RoVerGeNe | A tool for analysis of dynamical properties regarding genetic regulatory networks; RoVerGeNe is capable of robustness analysis and parameter constraint synthesis (sites.bu.edu/hyness/rovergene) | |
| BioPSy (Madsen et al. 2015) | Performs guaranteed parameter set synthesis for ODE biological models expressed in SBML given a desired behavior expressed by time-series data (github.com/dreal/biology) | |
| D-VASim | A genetic network simulator that is used to perform the timing and propagation delay analysis on genetic logic circuits; D-VASim supports SBML format (bda.compute.dtu.dk/tools-2/d-vasim) | |
| RoadRunner | A portable simulation engine for systems and synthetic biology models in SBML format; RoadRunner is written in C# and incorporates C, C++, and Python APIs (libroadrunner.org) | |
| Sequence editing | Benchling | Sequence repository capable of storing and showing annotations and searching; Benchling is also a cloud-based framework for life sciences applications (benchling.com) |
| ApE | A sequence editor supporting FASTA, GenBank, DNA Strider, EMBL, and ABI formats; it also supports direct connection to BLAST (biologylabs.utah.edu/jorgensen/wayned/ape) | |
| VectorEditor | Web-based DNA sequence-editing and analysis tool with restriction enzyme manager, amino acid translation, and gel digest prediction (public-registry.jbei.org/vectoreditor) | |
| GeneDesigner | Encompasses a set of in silico sequence design tools and algorithms, such as cloning, codon optimization, back translation and primer design; supports GenBank and FASTA formats (dna20.com/resources/genedesigner) | |
| VectorNTI/Express | Sequence analysis and design tool with an integrated graphical environment that provides the ability to manage, view, analyze, transform, share, and publish molecular biology data | |
| Geneious (Drummond et al. 2010) | Sequence editing and alignment tool with support for annotations, incorporating multiple alignment algorithms and easy switch between them (geneious.com/features/genome-alignment) | |
| GeneDesign | Web-based synthetic gene designer including various modules such as reverse translator, codon juggler, etc. for sequence manipulation (54.235.254.95/gd) | |
| Sequence REFINER (Chakrabarti et al. 2006) | Sequence alignment tool that refines a multiple sequence alignment by iterative realignment of its individual sequences with the predetermined conserved core model of a protein family (ftp.ncbi.nih.gov/pub/REFINER) | |
| SnapGene Editor | A sequence-editing software capable of creating, browsing, and sharing richly annotated DNA sequence files up to 1 Gb in length (snapgene.com) | |
| Synthetic Gene Designer (Wu et al. 2006) | Generates optimal gene sequences taking codon bias, like GC content, into consideration (userpages.umbc.edu/wug1/codon/sgd) | |
| SBOL Designer | CAD tool for creating and manipulating genetic construct sequences using the SBOL data model (async.ece.utah.edu/SBOLDesigner) |