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NEWS & ANALYSIS
GENOME WATCH
What has high-throughput sequencing ever done for us?
Julian Parkhill
This months Genome Watch looks back over the past 10 years and highlights how the incredible advances in sequencing technologies have transformed research into microbial genomes.
Genomics has always been a field in constant revolution, but the past decade has possibly seen the most radical changes to date. Ten years ago, microbial genome sequences were hand-crafted things, painstakingly sewn together and lovingly coloured in. Then, over the next few years, several technology companies came and parked their tanks on the lawns of the genome centres. Foremost of these were Solexa (now Illumina), Life Technologies and 454. The new sequencing technologies promised and delivered significantly higher throughput and lower cost, although the trade-off for this was shorter reads and a reduction in the cost-effectiveness of manual genome contiguation and correction, essentially mandating a strategic move from few finished genomes to many draft genomes.
Around the turn of the century, microbial genomes could take 1year or more to complete; generating the original shotgun data cost tens or hundreds of thousands of UK pounds, and therefore the manual effort involved in gap closure and error correction was worthwhile. Genomes for sequencing were chosen carefully, with the first projects focussing on pathogenic bacteria and culminating in the publication of a specific paper for each genome. Among the genomes published in 2003 were those of Porphyromonas gingivalis1, Bacillus anthracis2 and uropathogenic Escherichia coli3, each of which illustrates a key aspect of the state of microbial genomics at that time. P.gingivalis is a human oral pathogen associated with periodontal disease, and the analysis of the genome of strainW83 (REF.1) is a
good example of the importance of reference-genome sequencing. The genome allowed the reconstruction of the full metabolic capacity of the organism, and the identification of pathways and surface structures that might contribute to hostpathogen interactions and virulence. The key function of these initial projects was to generate reference data and hypotheses for further testing, and indeed this particular paper has been cited >175times, indicating its importance to the field.
The B.anthracis genome2 also represented a reference strain (Ames) and provided a similar overview of the physiology and virulence mechanisms of the organism, but in this...