A brief History of four Generations of Sequencing Technologies and their Impact on the World

Sequencing of the first human genome, completed in 2003, took over a decade and cost over a billion $. Technologies for sequencing nucleic acids have evolved tremendously since then. Radically new concepts have been developed, output and speed has increased, cost has decreased, and the way new generations of sequencing technologies are being applied enables applications that we could only dream of in 2003. In 2005, a second generation of sequencing technology was introduced. It used massively parallel processing of surface-bound DNA fragments and provided millions of short reads (50-200 bases) of a DNA input of interest. In 2010 this was followed by a third generation of sequencing technologies producing long reads of 10s of kilobases. By now the record for the longest single nucleic acid molecule sequenced is over 2 million bases. The cost of sequencing of a human genome has dropped to hundreds of Euros, and speed, accuracy and coverage allow the deployment for applications in health provision. At the same time a large palette of other applications using next-generation sequencing devices for readout, has sprung up and can be used to analyse transcriptomes, epigenomes and even do protein analysis. The sensitivity allows the analysis of the RNA in individual cells and studying cells in the context of their tissue. I will give an overview of the evolution of sequencing technologies and a glimpse at the application of next-generation sequencing in research and for the development of personalized medicine.