Comprehensive variation discovery in single human genomes

Our group has a new paper out (advance publication) at Nature Genetics called “Comprehensive variation discovery in single human genomes.” This paper was the result of a ton of effort, of which mine is only a part, and describes the earlier of our group’s two versions of the DISCOVAR genome assembly algorithm.

This Nature Genetics paper is an exploration of variant calling by assembly (as opposed to alignment), including extensive validation using finished Fosmid reference assemblies and selective Sanger sequencing. The combined variant caller/assembler is referred to as DISCOVAR, and works on either small genomes, or on regions of the human genome. We demonstrate that traditional alignment-based methods miss up to 25% of variants in a sample, with the misses largely concentrated, unsurprisingly, in areas of the genome that are challenging for alignment.

The current algorithm, called DISCOVAR de novo, is capable of de novo assembly of a mammalian genome in 24 hours (32 standard Xeon cores, 512 GB RAM) and will be the subject of an upcoming manuscript by our group.