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454, Roche to Launch New Instrument That Can Sequence Larger Genomes

NEW YORK (GenomeWeb News) - 454 Life Sciences and distribution partner Roche Diagnostics plan to release beta versions of a new sequencer later this year that they say will be better at sequencing larger genomes than the current Genome Sequencer 20, GenomeWeb News learned last week.
 
Separately last week, 454 and Roche introduced a new version of the GS20, which includes improved single-read accuracy, software algorithms that enable additional applications, new gasket formats, improved reagents, and a LIMS interface. 454 sold its first GS20 about a year ago.
 
But it is the new instrument that has whetted appetites in the sequencing community. That platform, to be called Genome Sequencer 100, is one of 10 "key" product launches Roche Diagnostics plans for 2006, CEO Severin Schwan told analysts last Wednesday during a first quarter earnings presentation in Switzerland. 
 
Burkhard Ziebolz, a spokesman for Roche Diagnostics in Germany, declined to give more information about the planned performance of the GS100 because it is still in development. However, he said the instrument, which will launch globally, is an "extremely important project" on which the partners are working "with a lot of force". He was unsure what quarter they plan to roll it out but said that it will probably appear "later in the year."
 
Bill Spencer, director of worldwide system sales for 454, told GenomeWeb News today that the companies will formally launch the GS100 sometime in 2007.
 
On the performance side, the GS100 is scheduled to provide 100 million bases of sequence data through a combination of longer reads and more reads, Spencer said.
 
Current GS20 users will be able to upgrade to the new instrument. "Programs are in development to ensure all users can take advantage of the newest technology," said Spencer. 454 has not decided whether it will continue to sell the GS20 once the GS100 has been launched.
 
Better How?
 
What could make the GS100 an instrument more suitable for sequencing larger genomes? GS20 users suggest one possible improvement would be paired-end information, which would help with repeat regions and contig assembly. In fact, 454 is scheduled to add those capabilities to the GS20 by July, the company said.
 
"All novel [DNA sequencing] platforms, to the best of my knowledge, lack paired-end sequencing, which likely will be necessary for larger genomes via [whole genome shotgun] approaches," Elaine Mardis, co-director of the Genome Sequencing Center at Washington University School of Medicine, and a GS 20 user, wrote in an e-mail to GenomeWeb News last week.
 
"Without pairing information, you can only assemble something where you have physical overlap of your reads, and the reads are relatively short, so the physical overlaps can't get you through repeats," said another GS20 user at a large genome sequencing facility who requested anonymity for fear of retribution from 454 if he inadvertently disclosed non-public information.
 
Pairing information can also help sort out the relationship between contigs. "And that's very important in terms of putting genome structure together," the user said. "It's really the difference between doing a survey of a genome and having an assembly of a genome."
 
454 has said in the past that it plans to add by the middle of this year support for paired reads, as well as software for mapping and assembling de novo genomes as large as 1 billion bases. In fact, 454 CEO Chris McLeod last week told investors during parent company CuraGen's first-quarter conference call that his company is "progressing on schedule to release" these improvements for whole-genome sequencing to the GS20.
 
According to Spencer, paired-end reads will become possible through a combination of a library protocol, reagents, and a revised assembler.
 
Another improvement to the GS20 would be longer reads, the unnamed GS20 user suggested. The GS20 currently produces 100-base reads, though the user told GenomeWeb News that he has seen data presented by 454 scientists at a conference where the instrument produced 200-base reads without affecting quality -- a "pretty impressive achievement," the user said. The company reached this performance through a mix of improvements in chemistry and informatics, he said.
 
Asked about his own interest in the new instrument, the unnamed user said he would "take one the day it's available," or even earlier if possible.
 
GS20 Upgrades
 
For the time being, the sequencing community will have to settle with an updated version of the GS20, which 454 and Roche introduced last week. The new version, GS20 1.02, consists of new software and reagents and is available at no additional cost to current users. It has a single read accuracy of at least 99 percent, which 454 claims will increase the quality of consensus sequences and improve the confidence level of putative sequence deviations. This improvement, from 98 to 99 percent, was achieved through software, according to the company.
 
Further, it includes new algorithms that improve sequence assembly and contig building. These algorithms will also facilitate sequencing of large number of short DNA fragments, like serial analysis of gene expression (SAGE) tags, cap analysis of gene expression (CAGE) tags, miRNA, or chromatin immunoprecipitation (ChIP) fragments, according to 454.
 
In addition, 454 added two more gasket formats for its PicoTiterPlate, which encompasses subdividing the plate to allow users to run different sequencing experiments in parallel.
 
454 also said it improved the shelf life of its reagents and their handling performance. For example, the reagents can now be thawed more rapidly.
 
Lastly, 454 has created a new LIMS interface that enables GS20 users more easily to attach the system to their Laboratory Information Management System.
 
454's McLeod also said during the call that the company is "on target" for the planned mid-year release of a so-called "ultradeep sequencing application," a new emPCR kit and software that will facilitate high resolution sequencing of targeted genes. The company's Measurement Services Center has already been using this new application as a service, and it already accounts for about half the business of the service unit, McLeod said. 
 
Roche and 454 are reluctant to reveal too much information about the GS100 because they do not want to risk undermining GS20 sales, which are going relatively well. For the first three months of the year --- the first full quarter during which Roche exclusively distributed the GS20 -- 454 generated nearly $4.5 million in revenue from instrument and reagent sales out of $9.3 million in total receipts. The company reported $2.4 million from sequencing services, and the remainder from milestones, royalties, and grants.
 
"We have been making   good strides in product sales as well as on the sequencing services side of our business," McLeod said during the call, adding that "we are well on track for the year's projection."

Julia Karow covers the next-generation genome-sequencing market for GenomeWeb News. E-mail her at GenomeWeb News. E-mail her at [email protected].

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