A paper published this week in PNAS provides a possible glimpse at the near-term future of next-gen sequencing technologies.

Susanne Goldberg, Justin Johnson, and colleagues at the J. Craig Venter Institute compared the cost of sequencing six marine microbial genomes using traditional Sanger sequencing chemistry (using an Applied Biosystems 3730xl), 454 Life Sciences? pyrosequencing-based approach, and a hybrid of the two. They observe that a hybrid strategy, blending 5.3x Sanger sequencing coverage with two rounds of 454 sequencing, typically produces a higher quality sequence than does sequencing to 8x coverage with Sanger chemistry alone (albeit at a cost increase of 10% to 20%), and suggest a 'two-tiered sequencing strategy' for future microbial sequencing projects.

'This hybrid sequencing strategy has the potential for being the first in years to have a major impact on the sequencing community,' the authors write. Indeed, they estimate the hybrid approach can reduce the cost of finishing a genome by up to 25%.

The news comes on the heels of an excellent June for 454, scientifically speaking. A study published June 25 in Nature Medicine demonstrated the utility of its pyrosequencing method to detect rare sequence variations in cancer biopsies, while a pair of studies earlier in the month used the technique to identify piRNAs.

Yet 454 evidently isn?t ready to dethrone Applied Biosystems, it seems. Citing short read lengths, accuracy concerns, and 'a lack of paired end reads,' the authors (none of whom is affiliated with either company) relegate 454 to a genomic clean-up role: 'We believe that most de novo sequencing projects should continue to rely primarily on Sanger sequencing data, while incorporating 454 sequencing data to use the complementary strengths of the 454 platform.'