Organizing genome engineering for the gigabase scale

Abstract

Genome-scale engineering holds great potential to impact science, industry, medicine, and society, and recent improvements in DNA synthesis have enabled the manipulation of megabase genomes. However, coordinating and integrating the workflows and large teams necessary for gigabase genome engineering remains a considerable challenge. We examine this issue and recommend a path forward by: 1) adopting and extending existing representations for designs, assembly plans, samples, data, and workflows; 2) developing new technologies for data curation and quality control; 3) conducting fundamental research on genome-scale modeling and design; and 4) developing new legal and contractual infrastructure to facilitate collaboration.

Fig. 1. As capabilities for genome engineering have advanced rapidly, the size of teams involved in each pioneering genome engineering project has also increased.

a From 1980 to present, the size of the largest engineered genomes has grown exponentially, doubling approximately every 3 years. This trend suggests that gigabase engineering could become feasible by 2050. b The number of authors credited with producing these genomes has also grown exponentially. This trend suggests that engineering gigabase genomes will require the effort of ~500 individuals—either directly as part of a team or indirectly through an ecosystem of tools, services, automation, and other resources. The data for this figure are provided in Table 1.

Fig. 2

The emerging design–build–test–learn workflow for genome engineering is shown schematically with current (solid arrows) and likely future (dashed arrows) tasks, interfaces (circles), and repositories (cylinders), either digital (light) or physical (dark).