Sarah Richardson, Johns Hopkins University School of Medicine
The execution of a synthetic genome project entails solving three major logistical problems. First, manipulations that are simple enough to be accomplished by manual editing at gene-scale become unreasonably involved if done by hand at genome-scale. Computational assistance is required for large and bulky genomes, but most biologists balk at using command-line tools. Second, as the project progresses there will be many versions of the synthetic genome, which must be carefully annotated and tracked to allow a “roll-back” in the case of lethal modifications. Finally, any project on a genome-scale involves many people from different technical backgrounds whose communication must be clear and whose efforts must be coordinated without redundancy. Concerned and interested members of the scientific community will also wish to suggest directions for the project, or monitor it for ethical reasons. Here we present progress towards solving all three problems with the development of BioStudio – a visual, open source platform for the computer-assisted multiscale design of synthetic genomes. BioStudio is both an integrated development environment and a genome version control system, with the ability to modify nucleotide sequences automatically or manually at multiple resolutions. It is currently able to locate and manipulate potential and existing restriction enzyme recognition sites, identify and incorporate unique sequences for PCR identification of wildtype and synthetic sequence, edit existing genome features, and create and annotate user-created genome features. Each version of the genome is encoded in a Gene Feature Format (GFF) file, which is then displayed by the open source annotation viewer GBrowse and stored in a branching version control system. Collaboration and transparency is accomplished through the use of a wiki. To ensure that BioStudio actually meets the needs of synthetic biologists, it is under development in support of the design and creation of a synthetic Saccharomyces cerevisiae genome.
Abstract Author(s): Sarah M. Richardson, Jessica S. Dymond, Jef D. Boeke, and Joel S. Bader