High-throughput sequencing for biology and medicine

Abstract

Advances in genome sequencing have progressed at a rapid pace, with increased throughput accompanied by plunging costs. But these advances go far beyond faster and cheaper. High-throughput sequencing technologies are now routinely being applied to a wide range of important topics in biology and medicine, often allowing researchers to address important biological questions that were not possible before. In this review, we discuss these innovative new approaches-including ever finer analyses of transcriptome dynamics, genome structure and genomic variation-and provide an overview of the new insights into complex biological systems catalyzed by these technologies. We also assess the impact of genotyping, genome sequencing and personal omics profiling on medical applications, including diagnosis and disease monitoring. Finally, we review recent developments in single-cell sequencing, and conclude with a discussion of possible future advances and obstacles for sequencing in biology and health.

Figure 1

Dimensionality of the genome. The understanding of the human genome has expanded with advances of sequencing technologies, from (A) 1D sequencing of the human genome to (B) 2D mapping of SVs using methods such as paired-end sequencing, (C) 3D genome-wide chromosomal conformation capture using ChIA-PET and Hi-C, and (D) four dimensions across time.

Figure 2

Sequencing technologies and their uses. Various NGS methods can precisely map and quantify chromatin features, DNA modifications and several specific steps in the cascade of information from transcription to translation. These technologies can be applied in a variety of medically relevant settings, including uncovering regulatory mechanisms and expression profiles that distinguish normal and cancer cells, and identifying disease biomarkers, particularly regulatory variants that fall outside of protein-coding regions. Together, these methods can be used for integrated personal omics profiling to map all regulatory and functional elements in an individual. Using this basal profile, dynamics of the various components can be studied in the context of disease, infection, treatment options, and so on. Such studies will be the cornerstone of personalized and predictive medicine.