Helicos Biosciences is reporting the sequencing of M13 in Science.
Helicos Biosciences is reporting the re-sequencing of the M13 viral genome.
What’s really cool about this is that it’s sequencing-by-synthesis, requiring no amplification before sequence reading, so there’s no biasing of the populations of DNA fragments. Here’s a short overview of how their sequencing by synthesis works:
So it’s still a shotgun-style technique, and the problem has been getting long enough read lengths to assemble the pieces into a whole sequence. Think of it like a jigsaw puzzle. The smaller the pieces are, the more you have that look identical, and the harder it is to figure out where to put them. Given 3 x 109 bases in the human genome, you’d need a read length of about 17 base pairs to be certain of ending up with all different pieces. They report average read lengths of 23 bp, with each individual sequence chunk represented about 150 times, and every part of the genome represented. This allows them to keep the error rate low enough that they could sequence different strains of the virus, and reliably pick up the genomic differences between the two. The paper doesn’t say how long this takes, but their marketing material says the process takes only one day.
The technique as practiced by Helicos has one major drawback, however, that will limit how low it can take the cost/base. It requires very expensive optics, since you’re essentially doing FRET on an array of targets. The list price for their instrument is $1.3 Million, with a consumables price of $18,000/sample, placing it out of reach of many institutions.
Illumina, another company with a sequencing-by-synthesis application, gets around the expensive optics issue by doing a clever solid-phase amplification of their target strands, essentially growing little colonies of identical strands in situ. A sales rep told me they’re selling around $500K, but didn’t have details on the consumables cost.
Long-term, I’d expect the Polonator to be the most widely adopted platform, due to their aggressive pursuit of royalty-free technology and low instrument cost. There’s a good thread to follow here, if you’re interested.
23andme and Navigenics take note: They’re not offering a direct to consumer service, yet, but there’s no way a SNP scan can compete with a full sequence, once the cost comes down.