5.01 The power of whole genomic sequencing in biomedical research and clinical applications

After the discovery of deoxyribonucleic acid (DNA) in the 1950s, the medical field has markedly changed. The first Sanger sequencing method used DNA synthesis machinery and four labels for the four dideoxynucleotides. Since then, second-generation sequencing methods such as Illumina, Ion Torrent, and SOLiD have replaced the first-generation. These methods rely on single nucleotide addition, cyclic reversible termination, sequencing by ligation, and real-time sequencing. They all produce readings of short sequences. In contrast, third-generation sequencing methods, such as PacBio and Nanopore, give long reads, making it possible to read long repetitive regions of the genome with a single run. While the first Sanger method took nearly 13years to complete reading the whole human genome, today's latest technologies can do the same in less than one hour. Such development has a significant clinical impact on cancer patients, enabling clinicians to guide personalized therapies based on molecular alterations in the patient's tissue detected via liquid biopsy. Interestingly, after the emergence of high-throughput sequencing (HTS) instruments for whole genome sequencing, diagnostic and predictive biomarkers have been discovered to help the treatment of complex diseases like cancer. The use of HTS revealed how nucleotide polymorphism, copy number variants, tumor mutation burden, microsatellite instability, and immune gene expression panels play an important role as biomarkers in cancer diagnosis and therapy. This chapter will describe the emergence of next-generation sequencing methods used for whole genome sequencing. A particular focus on cancer indicates their resourcefulness in the medical field.