RT Journal A1 Fiddes, Ian T. A1 Armstrong, Joel A1 Diekhans, Mark A1 Nachtweide, Stefanie A1 Kronenberg, Zev N. A1 Underwood, Jason G. A1 Gordon, David A1 Earl, Dent A1 Keane, Thomas A1 Eichler, Evan E. A1 Haussler, David A1 Stanke, Mario A1 Paten, Benedict T1 Comparative Annotation Toolkit (CAT)—simultaneous clade and personal genome annotation JF Genome Research JO Genome Research YR 2018 FD July 01 VO 28 IS 7 SP 1029 OP 1038 DO 10.1101/gr.233460.117 UL http://genome.cshlp.org/content/28/7/1029.abstract AB 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, ultracontiguous genome assemblies. To compare these genomes, we need robust methods for genome annotation. We describe the fully open source Comparative Annotation Toolkit (CAT), which provides a flexible way to simultaneously annotate entire clades and identify orthology relationships. We 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. We demonstrate the resulting discovery of novel genes, isoforms, and structural variants—even in genomes as well studied as rat and the great apes—and how these annotations improve cross-species RNA expression experiments.