Organizing genome engineering for the gigabase scale

TL;DR

This paper discusses the challenges and proposes strategies for scaling genome engineering to gigabase-sized genomes, emphasizing the need for standardized data exchange, new technologies, and collaborative frameworks.

Contribution

It identifies key challenges in large-scale genome engineering and offers specific recommendations for technological, methodological, and infrastructural advancements.

Findings

Current DNA synthesis enables megabase genome modifications

Genome-scale modeling informs metabolic network design

Coordination of data and workflows is a major challenge

Abstract

Engineering the entire genome of an organism enables large-scale changes in organization, function, and external interactions, with significant implications for industry, medicine, and the environment. Improvements to DNA synthesis and organism engineering are already enabling substantial changes to organisms with megabase genomes, such as Escherichia coli and Saccharomyces cerevisiae. Simultaneously, recent advances in genome-scale modeling are increasingly informing the design of metabolic networks. However, major challenges remain for integrating these and other relevant technologies into workflows that can scale to the engineering of gigabase genomes. In particular, we find that a major under-recognized challenge is coordinating the flow of models, designs, constructs, and measurements across the large teams and complex technological systems that will likely be required for gigabase genome engineering. We recommend that the community address these challenges by 1) adopting and extending existing standards and technologies for representing and exchanging information at the gigabase genomic scale, 2) developing new technologies to address major open questions around data curation and quality control, 3) conducting fundamental research on the integration of modeling and design at the genomic scale, and 4) developing new legal and contractual infrastructure to better enable collaboration across multiple institutions.