Sequencing in Precision Medicine

Sequencing is an integral part of today’s modern research. The first successful sequencing methods from the year 1977, which is today known as first-generation sequencing technologies (FGSTs), could be significantly improved at the beginning of the 21st century by the systemic improvements or by the introduction of new sequencing technologies otherwise known as next-generation sequencing technologies (NGSTs). These technologies enable scientists to achieve a significantly higher throughput compared with FGST, and thus, a considerable time and financial advantage is gained. Nevertheless, these NGSTs are also limited in their performance concerning the read length and the bias due to the mandatory sample amplification, which ultimately led to the introduction of third-generation sequencing technologies (TGSTs). In this chapter, various sequencing technologies, starting from FGSTs over NGSTs to TGSTs, are described giving basic information about the different key technologies, since most of them are still in use playing a major role in personalized medicine and genomic research. Starting with and since the human genome sequencing project, sequencing has gained prime importance in medical diagnostics, individualized (cancer) therapy, and theranostics, reaching out to almost any disease involving genetic factors and mutations. The latter, however, holds true for almost any disease beyond “monogenetic” diseases, including all complex and multifactorial diseases and syndromes such as neurodegenerative diseases, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis; also the most widely distributed coronary heart diseases and underlying diseases and risk factors such as diabetes, metabolic syndrome, blood pressure, and atherosclerosis; and the psychiatric diseases such as schizophrenia. More recent developments include sequencing of messenger RNA and noncoding RNA and potential diagnostic and theranostic biomarkers reflecting also the reactivity and susceptibility of an individual organism, offering also more tailored and individualized therapies. The technological development is key to progress in medicine, a fact held particularly true for sequencing methods. In this study, we want to give a brief overview of the history, technical features, and background of sequencing technology, emphasizing recent exciting and rapidly moving approaches in third-generation sequencing technology (TGST) and beyond.