Designing Combinatorial Libraries of Biological Systems

Double Dutch is a tool for designing combinatorial libraries of biological systems based on designs from response surface methodology (RSM). In practice, it is prohibitive to assemble and test millions of variants to determine how different DNA components affect the behavior of a pathway. RSM, however, provides the means to construct empirical models of system behavior without testing all variants. In RSM, a factorial design is the set of designs that tests how one or more “factors” affect a system of interest when taking on different combinations of quantitative “levels” chosen beforehand.

In order for RSM to be used in the context of genetic design, the genes and characterized DNA components that make up pathway variants must first be assigned to the factors and levels of a factorial design, respectively. Double Dutch uses heuristic algorithms, such as k-means clustering and simulated annealing, to optimize this assignment process with respect to three concerns, including the match between component parameters and design levels, the number of components repeated within each pathway (related to risk of homologous recombination), and the total number of unique components that must be synthesized to implement the pathway library.

Key Features

  • K-means clustering and simulated annealing-based assignment of characterized biosynthetic pathway modules to factorial designs

  • Ability to constrain solutions with predetermined module assignments.

  • Convert minimal expressions into logic gates, which represent available genetic circuits.

  • CSV import of DNA component library data plus grammar-based classification of this data into modules

  • CSV import of factorial designs from JMP and native generation of Plackett-Burman and Box-Behnken designs

  • CSV export of module assignments and resulting pathway libraries

Funding

  • This material is based upon work supported by the US Defense Advanced Research Projects Agency (DARPA) Living Foundries award HR0011-15-C-0084.

Double Dutch is free to use. Find the CAD website and GitHub located below:

Screen Shots

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