PT  - JOURNAL ARTICLE
AU  - Armstrong, Joel
AU  - Hickey, Glenn
AU  - Diekhans, Mark
AU  - Deran, Alden
AU  - Fang, Qi
AU  - Xie, Duo
AU  - Feng, Shaohong
AU  - Stiller, Josefin
AU  - Genereux, Diane
AU  - Johnson, Jeremy
AU  - Marinescu, Voichita Dana
AU  - Haussler, David
AU  - Alföldi, Jessica
AU  - Lindblad-Toh, Kerstin
AU  - Karlsson, Elinor
AU  - Zhang, Guojie
AU  - Paten, Benedict
TI  - Progressive alignment with Cactus: a multiple-genome aligner for the thousand-genome era
AID  - 10.1101/730531
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 730531
4099  - http://biorxiv.org/content/early/2019/08/09/730531.short
4100  - http://biorxiv.org/content/early/2019/08/09/730531.full
AB  - Cactus, a reference-free multiple genome alignment program, has been shown to be highly accurate, but the existing implementation scales poorly with increasing numbers of genomes, and struggles in regions of highly duplicated sequence. We describe progressive extensions to Cactus that enable reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality. We show that Cactus is capable of scaling to hundreds of genomes and beyond by describing results from an alignment of over 600 amniote genomes, which is to our knowledge the largest multiple vertebrate genome alignment yet created. Further, we show improvements in orthology resolution leading to downstream improvements in annotation.