RT Journal Article SR Electronic T1 Modeling CRISPR gene drives for suppression of invasive rodents JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.11.05.369942 DO 10.1101/2020.11.05.369942 A1 Samuel E. Champer A1 Nathan Oakes A1 Ronin Sharma A1 Pablo García-Díaz A1 Jackson Champer A1 Philipp W. Messer YR 2020 UL http://biorxiv.org/content/early/2020/11/06/2020.11.05.369942.abstract AB Invasive rodent populations pose a threat to biodiversity across the globe. When confronted with these new invaders, native species that evolved independently are often defenseless. CRISPR gene drive systems could provide a solution to this problem by spreading transgenes among invaders that induce population collapse. Such systems might be deployed even where traditional control methods are impractical or prohibitively expensive. Here, we develop a high-fidelity model of an island population of invasive rodents that includes three types of suppression gene drive systems. The individual-based model is spatially explicit and allows for overlapping generations and a fluctuating population size. Our model includes variables for drive fitness, efficiency, resistance allele formation rate, as well as a variety of ecological parameters. The computational burden of evaluating a model with such a high number of parameters presents a substantial barrier to a comprehensive understanding of its outcome space. We therefore accompany our population model with a meta-model that utilizes supervised machine learning to approximate the outcome space of the underlying model with a high degree of accuracy. This enables us to conduct an exhaustive inquiry of the population model, including variance-based sensitivity analyses using tens of millions of evaluations. Our results suggest that sufficiently capable gene drive systems have the potential to eliminate island populations of rodents under a wide range of demographic assumptions, but only if resistance can be kept to a minimal level. This study highlights the power of supervised machine learning for identifying the key parameters and processes that determine the population dynamics of a complex evolutionary system.Competing Interest StatementThe authors have declared no competing interest.