Contributed by Choli Lee - Shendure Lab - Department of Genome Sciences - University of Washington - Seattle, WA. The Illumina Genome Analyzer II (GA-II) performs massively parallel short-read DNA sequencing, with the potential to generate up to 10 gigabases in a single run. The technology provides researchers with a significantly cheaper alternative to conventional sequencing by capillary electrophoresis. A consistent and reliable method of DNA fragmentation is essential in Illumina library construction. We have evaluated and compared two types of fragmentation methods: nebulization and shearing using the Bioruptor.