Exome Sequencing

Exome workflow for the Ion Proton™ System

Exome Informatics Solutions

Torrent Suite™ Software coordinates all the experiment planning and data processing steps necessary to complete your exome sequencing workflow. New product templates enable users to plan exome runs simply and quickly. Raw data are processed on the Ion Proton™ Sequencer and transferred to the Proton™ Torrent Server for quality analysis and variant calling. The entire data analysis process only takes several hours and can be followed up by paired- or trio- sample exome analysis on the cloud-based Ion Reporter™ Software. Additional in-depth analyses can be performed with third-party software solutions such as the Ingenuity® Variant Analysis™ Knowledge Module for Ion Reporter™ Software.

Ion Reporter™ Software comprises a suite of bioinformatics tools that streamline and simplify analysis of semiconductor sequencing data. Data generated on the Ion Proton™ System are automatically uploaded from the Torrent Browser to the hosted Ion Reporter™ Software environment for read mapping, annotation, reporting of common and rare variants, and multi-sample analysis—all with version control and audit traceability.

The Ingenuity® Variant Analysis™ Knowledge Module for Ion Reporter™ Software helps researchers identify causal variants from exome data. Ingenuity® Variant Analysis™ Software can be accessed from within Ion Reporter™ Software to help identify, prioritize, and report the most biologically interesting variants for follow-up. Variant Analysis™ Software uses a series of filters that users can apply to quickly exclude common variants (based on the 1,000 Genomes Project) and nondeleterious variants, and then relate the remaining variants to biological relevance. The biological filtering in Variant Analysis™ Software is made possible by the rich biological content in the Ingenuity® Knowledge Base. Published findings about each variant of interest can be reviewed to assess the likely strength of its effect. Also, regulatory diagrams depicting how each variant may impact disease progression, with supporting literature, are readily accessible.

---

Exome Sequencing Basics

Understanding the variation present in the functionally important regions of a genome is vital to a multitude of genetic research questions. While whole genome sequencing (WGS) provides an optimal solution to variant identification, the combination of data analysis hurdles and the expense of WGS has led to the development and successful adoption of exome sequencing. Exome sequencing interrogates the interpretable part of a genome through enrichment strategies that target all coding regions of a genome, regulatory and 3’ untranslated regions, and other functionally annotated regions of interest such as miRNA genes and various noncoding RNAs. Importantly, for understanding human genetic disease, coverage includes regions implicated in inherited disorders as well as cancer-associated regions present in the COSMIC database.

Exome Sequencing Reveals Mutations and Indels

For genetic researchers, exome sequencing enables the identification of single-nucleotide variants and small insertions or deletions (indels) responsible for Mendelian diseases as well as rare de novo mutations that explain the heritability of complex diseases. Exome sequencing has already proven to be a powerful discovery tool, uncovering the causative mutations in a number of developmental disorders, neurological diseases, metabolic disorders, and inherited forms of vision loss and deficiencies of the blood and lymphatic system. Additionally, exome sequencing has provided fundamental insights into the genetic basis of cancer.

Solutions for Exome Sequencing

Exome sequencing effectively finds the middle ground between the completeness of WGS and the constraints of data analysis and the need to be cost-effective. Further, exome sequencing eliminates the time-consuming and costly need to sequence multiple genes and gene panels when attempting to discover rare variants of interest for diseases of unknown etiology. Consider the following solutions to begin cost-effective, scalable exome sequencing studies in your lab:

• The Ion Proton™ System enables sequencing of 1–2 exomes per run with the Ion PI™ Chip and will enable higher multiplexing with the Ion PII™ Chip*
• Ion TargetSeq™ Exome Kits offer a simple and flexible workflow that allows sample multiplexing with up to four samples in a single target-enrichment reaction
• Intuitive and simple data analysis using Ion Reporter™ Software for the annotation of common and rare variants

The Ion Proton™ System, combined with Ion TargetSeq™ technology and Ion Reporter™ Software, delivers fast, flexible, and high-quality exome sequencing that scales with your research needs. Go from exome library to variant identification in a single day.

*The content provided herein may relate to products that have not been officially released and is subject to change without notice.
*†Ion Chef™ System is expected to be available for quotation and purchase in Q1 2013 and is expected to begin shipping in the first half of 2013.

For Research Use Only. Not for use in diagnostic procedures.