Next-Generation Sequencing: A Revolutionary Tool for Toxicogenomics

Over the past five years, DNA sequencing has been undergoing fundamental changes due to the rapid development of next-generation sequencing (NGS) technologies. NGS technologies have been offering unprecedented opportunities for high-throughput functional genomic research, and opening up new fields and novel applications in biology, life sciences, and biomedicine. The major advantages of NGS technologies over conventional Sanger sequencing include sequencing cost reduction from about 0.50 per kilobase to as little as 0.001 per kilobase, and massive parallelism that dramatically increases sequencing throughput. However, Sanger-based approaches provide advantages in terms of read-length and base call accuracy. In this chapter, we first describe the fundamental principles of four currently commercialized NGS platforms from Roche/454, Illumina, Life Technologies, and Helicos BioSciences. Next we discuss the challenges in analyzing short reads from NGS, and outline major applications of these new technologies. Finally, we compare data between NGS and microarrays with a toxicogenomics study aiming at gene expression profiling. Keywords: next-generation sequencing (NGS); ultra high-throughput sequencing; RNA-Seq; ChIP-Seq; transcriptome; toxicogenomics; sequence alignment