Automated Design of Assemblable, Modular, Synthetic Chromosomes

Sarah Richardson, Johns Hopkins University School of Medicine

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The goal of the Saccharomyces cerevisiae v2.0 project is the complete synthesis of a re-designed genome for baker’s yeast. The resulting organism will permit systematic studies of eukaryotic chromosome structure that have been impossible to explore with traditional gene-at-a-time experiments. The efficiency of chemical synthesis of DNA does not yet permit direct synthesis of an entire chromosome, although it is now feasible to synthesize multi-kilobase pieces of DNA that can be combined into larger molecules. Designing a chromosome-sized sequence that can be assembled from smaller pieces has to date been accomplished by biological experts in a laborious and error-prone fashion. Here we pose DNA design as an optimization problem and obtain optimal solutions with a parallelizable dynamic programming algorithm.

Abstract Author(s): Sarah M. Richardson, Brian S. Olson, Jessica S. Dymond, Randal Burns, Srinivasan Chandrasegaran, Jef D. Boeke, Amarda Shehu, and Joel S. Bader