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ABI Ships Initial SOLiD Units; Stanford First, Agencourt and Others to Follow

Applied Biosystems has started the early-access program for its SOLiD next-generation sequencer after shipping “initial units” of the instrument to “leading research institutions,” and has started accepting orders from other early-access customers.
A group of researchers at Stanford University, which already owns a 454 Genome Sequencer, will be the first recipient, while Agencourt Bioscience expects to receive an instrument “shortly,” In Sequence has learned.
In addition, the Joint Genome Institute, Washington University, Baylor College of Medicine, the Genome Institute of Singapore, and the University of Kiel in Germany are expecting to receive instruments under the early access program, representatives of these institutions told In Sequence.
ABI also said it is developing applications for the SOLiD system with a number of research institutions, including Stanford University, the Broad Institute, the Wellcome Trust Sanger Institute, Baylor College of Medicine, the Joint Genome Institute, the University of Queensland, and Washington University, “among others.” ABI did not say if any of these groups will also receive an instrument.
ABI, which becomes the third company to ship next-generation sequencers after 454 Life Sciences, which sold its first instruments in early 2005, and Solexa, which shipped its first machines about a year ago, expects to use feedback from the early-access customers to improve its system.
“Realistically, I don’t think any corporate R&D facility is able to test a product to the same degree that a customer is,” Kim Caple, ABI’s vice president and general manager of the genetic analysis high-throughput discovery business unit, told In Sequence last week. “They have access to the samples, they have the projects, they have the benefit of a real lab workflow and being able to really figure out how a technology fits.”
Based on customer results, ABI plans to “further develop the system and really deliver to the marketplace what the customer wants,” she said.
The Stanford researchers already have ideas for how to use the instrument. They are getting their machine as part of a sequencing initiative organized by the departments of pathology and genetics at the Stanford Medical School, which decided to acquire both an Illumina Genetic Analyzer and a SOLiD system, according to Arend Sidow, an associate professor with an appointment in both departments.
Sidow’s group has been receiving data from the SOLiD system from a collaboration with ABI to analyze nucleosome positioning in C. elegans (see In Sequence 2/13/2007), and “we felt it was a unique opportunity to be among the first ones to work with it directly,” he told In Sequence by e-mail this week.
Several faculty members with “diverse research interests” will be using the instrument for a variety of projects, he said, among them gene expression in cancer and in stem cells, microRNA diversity in certain tissues, transcription factor occupancy of regulatory regions, nucleosome positioning in complex genomes, and genomic natural variation in populations.
Initially, the SOLiD will be housed “in departmental space close to my lab,” he said.
Meantime, George Weinstock, co-director of Baylor College of Medicine’s Human Genome Sequencing Center, said data from the platform helped him and his colleagues to correct a Sanger-based assembly of a bacterial strain.

“Because coverage with a sequencing platform like the SOLiD is so much higher, [and] you get so many more reads to work with, [events like large-scale duplications] tend to really stand out.”

Researchers at his center recently sequenced E. coli strain DH10B using capillary sequencing in order to find out why it, unlike other E. coli strains, can be efficiently transformed with large DNA fragments.
Based on a preliminary assembly that the Baylor team posted online, ABI researchers decided to sequence the same strain on their SOLiD platform. After deciding to collaborate, Weinstock sent them his finished assembly, onto which they mapped the SOLiD reads.
Paired-end SOLiD reads indicated that there was a 100-kilobase duplication in the genome, which had collapsed in the Sanger assembly.
“We went back and looked at our assembly data, and sure enough, there were indications that the number of reads that had been assembled in this region was higher than elsewhere,” Weinstock said. “And then when we looked harder, we did find in fact some of our read pairs, from Sanger sequencing, that supported the idea that this should be separated.”
The reason the Sanger assembly missed the duplication was that the coverage was not high enough. “Maybe a more sensitive assembly algorithm …might have done it,” Weinstock suggested. But “because coverage with a sequencing platform like the SOLiD is so much higher, [and] you get so many more reads to work with, these things tend to really stand out,” he said.
“So we were quite pleased with that. It allowed us to correct the assembly and get it right,” he added. His team is planning to publish the results in two separate papers, one focusing on the assembly and the role of the SOLiD data, the other one on the biology.

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