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The sequencing by oligonucleotide ligation and detection (SOLiD) system being commercialized by Applied Biosystems generates sequences of randomly generated fragment or mate-paired DNA molecules utilizing a novel ligation-based chemistry and fluorescent probe pools. Consistent improvements have been made in total sequence throughput per run by enhanced read length and base calls, higher bead densities per array, and increased frequency of assignable reads. In combination, these improvements have allowed progressively deeper sequencing coverage of more complex model organisms. To date, we have sequenced, to varying depths of coverage, the genomes of several bacterial genomes. In addition to whole genome sequencing, we have developed a workflow to allow targeted resequencing and are working with collaborators to develop tag-based sequencing applications. Improvements to the SOLiD sequencing technology and the impact on the increased sequencing throughput as they apply to a number of different applications will be presented.