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Roche to Launch Scaled-Down 454 Sequencer in 2010; JGI First Test Site for Long GS FLX Reads


By Julia Karow

This article was originally published Nov. 19.

454 Life Sciences said two weeks ago that it plans to launch a scaled-down, "desktop" version of its Genome Sequencer system next year.

The system, called GS Junior, will have a lower price and throughput than the current GS FLX but offer the same read length of 400 to 500 bases. Later this month, 454 plans to start early-access testing for the Junior, as well as for an upgrade to the FLX that will enable reads of up to 1 kilobase for that platform.

According to a company spokesperson, the GS Junior will cost about a fourth to a fifth of the GS FLX, which has a list price on the order of $500,000. It will generate about a tenth of the output, or more than 35 megabases of data and an average of 100,000 reads per 10-hour run. Both the PicoTiterPlate and the camera will be smaller than those of the FLX.

The Junior will use the same pyrosequencing chemistry that runs on the FLX. The cost per base will be "in the same range" as that for the GS FLX, according to the spokesperson.

In contrast to the FLX, which requires a compute cluster, the Junior will ship with a desktop computer that is optimized for processing and analyzing 454 data. Library and sample prep will be the similar in principle to the FLX but due to the smaller scale will not require the specialized equipment that the FLX does.

Like the FLX, the Junior will be for research use only.

454 said it plans to ship the first Junior instruments to a handful of early-access customers in late November, followed by a full commercial launch in the spring or early summer of next year.

According to Michael Egholm, 454's chief technology officer and vice president of R&D, the GS Junior is aimed at individual researchers who have found the price tag of the FLX to be too high and who have smaller projects that do not require the data output of the GS FLX.

The Junior, he said, will fill a niche opposite the high-throughput sequencing market that has been largely occupied by Illumina's Genome Analyzer and Applied Biosystems' SOLiD. That lower-throughput end of the market — currently served by Sanger sequencers — "we believe is a much bigger market, [and] nobody has had an offering until this," Egholm told In Sequence two weeks ago.

With the new instrument, "we are going to lower the threshold dramatically for the number of genes and the number of samples you need before it makes sense to analyze them on the 454 technology," he said.

While the GS FLX has been most successful outside of genome centers, he said, the price of the instrument and ancillary equipment, as well as the run costs, have largely kept it outside labs with small budgets. This, he predicted, will change with the GS Junior, which 454 anticipates will penetrate a large number of labs.

"For this to make sense economically, we are going to sell an order of magnitude more of these instruments than the FLX," Egholm said. "We certainly think the market size and the number of customers that want to make use of this is of that order, or we would not have done this."

The instrument might also be of interest to existing FLX customers, as well as to users of short-read sequencing platforms, he said. "I think it would be reasonable to expect that these guys, who also need a long-read technology, go ahead now and buy this because it's now a reasonably sized investment," Egholm said.

Besides being smaller — the instrument is "the size of a laser printer," according to 454 — the data analysis is also more user-friendly, "so people who are not trained in bioinformatics can do bioinformatics," he said.

Data processing takes places on the "souped-up" PC that comes with the instrument, according to Egholm, which has GUI-based data analysis software pre-installed, including a de novo assembler, a reference mapper, and an amplicon variant analyzer. "There is no need for command-line instructions or a costly high-end computing cluster," according to the company's website.

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Sample prep for the GS Junior is essentially the same as for the GS FLX, which involves emulsion PCR, but because the PicoTiterPlates are smaller, protocols for the ePCR have been "greatly simplified," Egholm said. Three pieces of ancillary equipment for sample prep for the GS FLX are not required for the Junior. "All you need is, essentially, standard laboratory equipment," Egholm said.

Specifically, a bead counter that can cost $20,000 or more, he said, has been replaced by a "simple device" to measure the bead volume. Also, instead of a tissue lyser to make the emulsion a "small mixer" that costs on the order of $1,000 can be used. Finally, because the PicoTiterPlate is smaller, it fits into a standard micro-centrifuge, whereas the larger FLX plates require a non-standard centrifuge.

Sample prep will also benefit from recent improvements for both the FLX and the Junior, for example a new library preparation kit that 454 launched this week.

A sequencing experiment on the GS Junior, including sample preparation, can be completed "well within 24 hours," Egholm said, a feature the company plans to demonstrate more extensively prior to the commercial launch.

The company has already rerun on the Junior samples from a previous collaboration with Columbia University's Ian Lipkin, who is expected to become one of the first early-access customers for the instrument.

In terms of applications, Egholm said that the Junior will be most suitable for smaller projects. "The conundrum we have is that the FLX has way too much throughput for many laboratories for many applications," he said.

More specifically, in terms of whole-genome sequencing projects, "if you want to de novo sequence insect genomes and [genomes] up [in size], the FLX makes sense. If you do bacterial sequencing, the Junior makes a lot of sense," he said.

The instrument is also suitable for more targeted sequencing projects, such as human leukocyte antigen, VDJ-region sequencing, or HIV sequencing, he added. "In order to do these economically on the FLX, you need hundreds of samples …but for the typical laboratory, you want to do 16, 24, or 48 samples, and the GS Junior fits really perfectly for that."

GS FLX: Intercepting Sanger

The key differentiator between the GS Junior and the GS FLX — besides throughput and price — will be the availability of longer reads up to 1,000 base pairs in size for the FLX, which 454 will start testing at its first early-access customer site — the Department of Energy Joint Genome Institute — later this month. "We are only engineering a solution for that for the FLX," Egholm said.

The long-read chemistry will require a hardware modification of the instrument, which needs to transport twice as much fluid as before, he explained, as well as software and script updates and some other, unspecified improvements "to get the performance up." A spokesperson said that the cost of the upgrade "will be attractive as we want to encourage its use." Roche has previously said that the long reads will be launched fully sometime next year.

With reads up to 1,000 base pairs, Egholm said, the company will be "definitely intercepting the read length and quality of Sanger sequencing reads now."

Other companies are also planning to enter the long-read sequencing market, among them Pacific Biosciences, which plans to launch an instrument during the second half of 2010 that will initially offer Sanger-length reads of lower quality, and Illumina, which acquired Avantome last year to develop a long-read sequencing platform.