Next-generation sequencing (NGS): A revolutionary technology in pharmacogenomics and personalized medicine

Abstract

Personalized medicine can improve healthcare by selecting treatments that are more efficacious or induce less adverse responses in stratified cohorts sharing differentiating genetic traits. Personalized medicine has advanced quickly, providing both opportunities and challenges for the pharmaceutical industry and regulatory agencies in the twenty-first century. Pharmacogenomics is the key to the identification of personalized medicine biomarkers useful for efficacy and safety that can ultimately be clinically applied for diagnosis, prognosis, and treatment selection. The requisite technologies and approaches needed for pharmacogenomics have steadily advanced over more than a decade in terms of both capability and cost. In 2005, 454 Life Sciences announced their sequencing-by-synthesis technology, the first next-generation sequencing (NGS) platform, proclaiming the breakthrough in sequencing technology. NGS is revolutionizing pharmacogenomics and personalized medicine, with several NGS platforms commercially available. Illumina, Roche 454, and Applied Biosystems are the current major vendors. This chapter will characterize the technical assessments of NGS, including comparative analyses across platforms, experimental protocols, algorithms for mapping short reads to reference genomes, strategies for quantitatively measuring expression levels, and methods for detecting single nucleotide polymorphisms (SNPs). Different pipelines and software packages for analyzing NGS data will be reviewed. Examples and a prospective outlook on applications of NGS in pharmacogenomics and personalized medicine will be given.