A Taxonomic and Phylogenetic Classification of Diverse Base Editors.

Abstract

Base editors mediate the targeted conversion of single nucleobases in a therapeutically relevant manner. Herein, we present a hypothetical taxonomic and phylogenetic framework for the classification of more than 200 different DNA base editors, and we categorize them based on their described properties. Following evaluation of their in situ activity windows, which were derived by cataloguing their activity in published literature, organization is done hierarchically, with specific base editor signatures being subcategorized according to their on-target activity or nonspecific, genome- or transcriptome-wide activity. Based on this categorization, we curate a phylogenetic framework, based on protein homology alignment, and describe a taxonomic structure that clusters base editor variants on their target chemistry, endonuclease component, identity of their deaminase component, and their described properties into discrete taxa. Thus, we establish a hypothetical taxonomic structure that can describe and organize current and potentially future base editing variants into clearly defined groups that are defined by their characteristics. Finally, we summarize our findings into a navigable database (ShinyApp in R) that allows users to select through our repository to nominate ideal base editor candidates as a starting point for further testing in their specific application.