Double Dutch: A Tool for Designing Combinatorial Libraries of Biological Systems.
Recently, semirational approaches that rely on combinatorial assembly of characterized DNA components have been used to engineer biosynthetic pathways. In practice, however, it is not practical to assemble and test millions of pathway variants in order to elucidate how different DNA components affect the behavior of a pathway. To address this challenge, we apply a rigorous mathematical approach known as design of experiments (DOE) that can be used to construct empirical models of system behavior without testing all variants. To support this approach, we have developed a tool named Double Dutch, which uses a formal grammar and heuristic algorithms to automate the process of DOE library design. Compared to designing by hand, Double Dutch enables users to more efficiently and scalably design libraries of pathway variants that can be used in a DOE framework and uniquely provides a means to flexibly balance design considerations of statistical analysis, construction cost, and risk of homologous recombination, thereby demonstrating the utility of automating decision making when faced with complex design trade-offs.
Department of Electrical and Computer Engineering, Boston University , Boston, Massachusetts 02215, United States.
Nicholas
N
Roehner
Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Eric M
EM
Young
Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Christopher A
CA
Voigt
Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
D Benjamin
DB
Gordon
Department of Electrical and Computer Engineering, Boston University , Boston, Massachusetts 02215, United States.
Douglas
D
Densmore
D000465:Algorithms; D053898:Biosynthetic Pathways; D015723:Gene Library; D012984:Software; D058615:Synthetic Biology / Q000379:methods*; D057188:Workflow