The development and impact of 454 sequencing

Nat Biotechnol. 2008 Oct;26(10):1117-24. doi: 10.1038/nbt1485.


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.

MeSH terms

  • Chromosome Mapping / instrumentation*
  • Equipment Design
  • Equipment Failure Analysis
  • Genome, Human / genetics*
  • Genomics / instrumentation*
  • Humans
  • Sequence Analysis, DNA / instrumentation*
  • Sequence Analysis, DNA / methods
  • Technology Assessment, Biomedical