Glimpse-crick

Since the fundamental discovery of the structure of DNA (128) and the pioneering development of methods to detect the sequence of DNA bases by foundational approaches such as Maxam & Gilbert's technique (76) and Sanger sequencing (106), the field of DNA sequencing has rapidly evolved in capacity, capability, and applications. As with many technologies, advances across multiple fields were brought together to achieve routine sequencing at the genome scale. The development of the polymerase chain reaction (103, 104), the widespread availability of high-quality nucleic acid–modifying enzymes, and the development of fluorescent automated DNA sequencing enabled the Human Genome Project to deliver the first draft of the human genome sequence in 2001 (64, 123) and the first completed draft three years later (54). Since then, genomics has evolved at an amazing pace. Dozens of next-generation sequencing companies and technologies have been created, and the corresponding field of bioinformatics has exploded as a major scientific and training discipline. DNA sequence has even been proposed as a highly efficient storage mechanism for large-scale data (22).

The progression from the discovery of the structure of DNA to the ability to sequence it as a routine assay has had several inflection points. In the mid-to-late 1990s, microarrays were developed as highly parallel assays to measure RNA and DNA (91, 107). Between 2001 and 2006, microarrays offered the first genome-scale parallel analysis of DNA and RNA. In 2006, second- and third-generation sequencing techniques began to emerge that permitted an unbiased means to examine billions of templates of DNA and RNA. Although now almost a decade old, the term next-generation sequencing remains the popular way to describe very-high-throughput sequencing methods that allow millions to trillions of observations to be made in parallel during a single instrument run.

Since 2006, there has been an explosion of new methods, techniques, and protocols for the examination of virtually any question in basic genetics or clinical research involving nucleic acid. The rapid evolution of instruments, chemistries, and techniques led to next-generation sequencing instruments changing within months and chemistries and analysis algorithms changing within weeks, creating substantial challenges for both researchers and clinicians. The challenges arising from such rapid changes were amplified by a lack of widely available biological and biochemical standards and public data sets to assess these nascent technologies and methods. Over the last few years, technology platforms have been used and tested across a broad user market in a wide variety of research projects, helping the methods and instruments to mature and enabling a diversity of publications, methods, and applications of sequencing technology. Thousands of application, technical, informatic, and translational articles have been published that describe the use of sequencing technologies, with many hundreds more added each year.

Several excellent reviews over the last several years have described the technological landscape of sequencing (78, 80, 96). When examined in chronological order, these and other examples provide a superb history of the changing sequencing space and the amazing pace that has brought us from the first draft of the human genome sequence to the ability to routinely sequence human genomes with widely available technology at a cost decreasing from billions of dollars to thousands of dollars in less than 25 years. Table 1 summarizes the past, present, and future of commercially launched sequencing platforms and their original references.