Solexa sequencing: decoding genomes on a population scale.

Abstract

It is has now been some 17 years since David Klenerman and I (Fig. 1) conceived a project that would subsequently enable rapid whole human genome sequencing. The core thinking that led to Solexa Sequencing was sparked by observations made during basic exploratory research carried out in our laboratories during the mid to late 1990s, and the redirection of these observations toward DNA sequencing was an unintended consequence. The founding ideas and proof-of-concept experiments were carried out at the University of Cambridge. The first commercial sequencing system was subsequently developed at Solexa Limited, a company we founded in 1998. Illumina Inc. acquired Solexa in early 2007 and made further improvements that led to several new sequencing systems. Today, the technology is being used to routinely decode human genomes for medical research, clinical decision-making, and basic science, all at a cost and speed that make population-scale sequencing practical. The journey from concept to reduction to practice has already gone beyond my expectations in terms of performance, adoption, and early insights, yet the era of clinical whole genome sequencing is perhaps only just beginning. Fig. 1. David Klenerman and me at our “local,” where we have enjoyed much creative discussion (and beer). In the mid-1990s, in the University Chemical Laboratories, Cambridge, David Klenerman and I were using fluorescence single-molecule spectroscopy to observe the synthesis of DNA by a polymerase enzyme using fluorescently encoded nucleotides. The work itself and the grant proposal that supported it were fundamental in nature and said nothing of sequencing. The struggle and attempts to improve the experimental design to optimize what we wished to observe suggested to us a means to decode a strand of immobilized DNA by single-molecule fluorescence imaging. It was not immediately clear what the benefits of decoding DNA on a surface would be, until our awareness of DNA microarrays prompted the realization that the decoding of immobilized DNA could be made parallel …