Perspective abstract

Focus on Next-Generation Sequencing


Nature Biotechnology 26, 1117 - 1124 (2008)
Published online: 9 October 2008 | doi:10.1038/nbt1485

The development and impact of 454 sequencing

Jonathan M Rothberg1 & John H Leamon2


The 454 Sequencer has dramatically increased the volume of sequencing conducted by the scientific community and expanded the range of problems that can be addressed by the direct readouts of DNA sequence. Key breakthroughs in the development of the 454 sequencing platform included higher throughput, simplified all in vitro sample preparation and the miniaturization of sequencing chemistries, enabling massively parallel sequencing reactions to be carried out at a scale and cost not previously possible. Together with other recently released next-generation technologies, the 454 platform has started to democratize sequencing, providing individual laboratories with access to capacities that rival those previously found only at a handful of large sequencing centers. Over the past 18 months, 454 sequencing has led to a better understanding of the structure of the human genome, allowed the first non-Sanger sequence of an individual human and opened up new approaches to identify small RNAs. To make next-generation technologies more widely accessible, they must become easier to use and less costly. In the longer term, the principles established by 454 sequencing might reduce cost further, potentially enabling personalized genomics.

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  1. Rothberg Institute for Childhood Diseases, 530 Whitfield Street, Guilford, Connecticut 06437, USA.
  2. Ion Torrent Systems, 37 Soundview Road, Guilford, Connecticut 06437, USA.

Correspondence to: Jonathan M Rothberg1 e-mail: jrothberg@childhooddiseases.org



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