Comparative Annotation Toolkit (CAT) - Simultaneous Clade and Personal Genome Annotation

The recent introductions of low-cost, long-read and read-cloud sequencing technologies coupled with intense efforts to develop efficient algorithms have made affordable, high-quality de-novo sequence assembly a realistic proposition. The result is an explosion of new, ultra contiguous genome assemblies. To compare these genomes we need robust methods for genome annotation. I describe the fully open source Comparative Annotation Toolkit (CAT), which provides a flexible way to simultaneously annotate entire clades and identify orthology relationships. I show that CAT can be used to improve annotations on the rat genome, annotate the great apes, annotate a diverse set of mammals, and annotate personal, diploid human genomes. I demonstrate the resulting discovery of novel genes, isoforms and structural variants, even in genomes as well studied as the rat and great apes, and how these annotations improve cross-species RNA expression experiments.