Abstract

The presentation will give an overview of Illumina’s high throughput / high quality sequencing technology with the Genome Analyzer IIx system and software architecture. It will then illustrate algorithms in the CASAVA Framework used to call structural variation events on genomes of all size ranges to ensure improved sensitivity and specificity. The remainder will focus on results obtained with the new framework applied to Cancer research explained in more detail below.

Accurate and rapid sequencing of individual human cancer genomes paves the way to discover the full catalogue of somatic mutations that underlie the molecular basis of tumorigenesis. In collaboration with the Wellcome Trust Sanger Institute, we have sequenced both tumour and normal genomes from a malignant melanoma cell line, with the aim of identifying somatic variants in the cancer sample. The tumour and normal were sequenced on the Illumina Genome Analyzer II system to 40x and 30x depth respectively.

In order to identify somatic events, we employed strict variant calling criteria in the tumour sample and subtracted a more permissive set of variant calls from the normal, identifying more than 30,000 single base substitutions and other events such as short indels, structural variants and copy number changes. This study illustrates the precision of somatic mutation detection in whole genome sequencing and the feasibility for large-scale studies to identify novel genetic elements that are involved in tumorigenesis and may be used as diagnostic markers.