PMID- 27110633 OWN - NLM STAT- MEDLINE DCOM- 20170306 LR - 20170306 IS - 2161-5063 (Electronic) IS - 2161-5063 (Linking) VI - 5 IP - 6 DP - 2016 Jun 17 TI - Double Dutch: A Tool for Designing Combinatorial Libraries of Biological Systems. PG - 507-17 LID - 10.1021/acssynbio.5b00232 [doi] AB - 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. FAU - Roehner, Nicholas AU - Roehner N AD - Department of Electrical and Computer Engineering, Boston University , Boston, Massachusetts 02215, United States. FAU - Young, Eric M AU - Young EM AD - Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States. FAU - Voigt, Christopher A AU - Voigt CA AD - Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States. FAU - Gordon, D Benjamin AU - Gordon DB AD - Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States. FAU - Densmore, Douglas AU - Densmore D AD - Department of Electrical and Computer Engineering, Boston University , Boston, Massachusetts 02215, United States. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20160503 PL - United States TA - ACS Synth Biol JT - ACS synthetic biology JID - 101575075 SB - IM MH - *Algorithms MH - Biosynthetic Pathways MH - Gene Library MH - *Software MH - Synthetic Biology/*methods MH - Workflow EDAT- 2016/04/26 06:00 MHDA- 2017/03/07 06:00 CRDT- 2016/04/26 06:00 PHST- 2016/04/26 06:00 [entrez] PHST- 2016/04/26 06:00 [pubmed] PHST- 2017/03/07 06:00 [medline] AID - 10.1021/acssynbio.5b00232 [doi] PST - ppublish SO - ACS Synth Biol. 2016 Jun 17;5(6):507-17. doi: 10.1021/acssynbio.5b00232. Epub 2016 May 3.