This article has been updated from a previous version to clarify the Broad's prior installed base of SOLiDs. The institute had three systems, not two as initially reported.
As Illumina and Applied Biosystems compete to win market share for their respective short-read, high-throughput sequencing platforms, two of the largest genome centers in the world are scaling up.
Last week, Illumina said that the Wellcome Trust Sanger Institute has purchased 11 Illumina Genome Analyzers, adding to the 26 GAs it currently has installed, while ABI said the Broad Institute will add five ABI SOLiD systems to its installed base of three SOLiDs.
The two centers have been among the earliest testers of both short-read sequencing platforms, and research institutes becoming interested in the new technologies are likely paying close attention to the choices they make and why they made them.
Illumina’s Genome Analyzer, which came to market about two years ago under the Solexa brand, currently has an edge at large genome centers; as of last month, about four times more GAs than SOLiDs were installed at a number of genome centers around the world (see In Sequence 10/7/2008). But ABI, which launched its SOLiD sequencer a year ago, says it is catching up.
Sanger’s addition of 11 GAs makes its fleet probably the largest single installation of this instrument type anywhere. The institute also currently has five ABI SOLiD machines and two 454 Genome Sequencer FLX instruments.
According to the Sanger, the GA and SOLiD perform equally well at a similar cost, but the main reason it decided to scale up its Illumina base is that it already had sample prep and informatics pipelines set up for this platform.
Meantime, the Broad Institute will add five additional SOLiD systems to the three it currently has in place. As of last month, the Broad also had on site 20 Genome Analyzers, 10 GS FLXs, and one Polonator.
The Broad plans to use the new instruments to study cancer. In a statement, ABI quoted Chad Nusbaum, co-director of the Broad’s genome sequencing and analysis program, as saying that “We are excited to further test SOLiD’s accuracy rate and throughput capabilities on these important cancer genome projects.”
In response to a request for comment on the SOLiD additions, Rob Nicol, director of sequencing operations at the Broad, talked about the institute’s mission to test new technologies. “As lead users, our goal is to shake out these prototype technologies in partnership with the manufacturers to establish their value, develop applications, make them reliable, and easy to implement in the larger community,” he said in an e-mail message.
“Because of this development role, our decisions are different than ones a researcher strictly looking for an efficient and robust sequencing solution might make.” Rapid changes in the technology require “continuous evaluation and optimization at the minimum efficient scale” required by large-scale sequencing projects, he added.
It is unclear whether the Broad Institute also considers adding more Genome Analyzers in the near future.
Sanger’s ‘Difficult’ Choice
The Sanger Institute, after deciding “some time ago” that it wanted to scale up its capacity for second-generation sequencing, subjected its Illumina and ABI sequencers to “fairly extensive” testing, according to Julian Parkhill, director of sequencing at the institute.
“What we came up with after looking at it in house, and also talking to the manufacturers about potential future developments, is that there really wasn’t a great deal to choose between them,” he said. “They have very similar accuracies, they have very similar throughputs, they have very similar costs. And on those bases, it would be very difficult to make a decision between them.”
“They have very similar accuracies, they have very similar throughputs, they have very similar costs.”
In the end, the institute decided that it would be easier and cheaper to fit additional instruments into its existing pipelines for the Illlumina platform than to build a new pipeline for SOLiD. “The marginal incremental cost of putting in further Illuminas is a lot lower than the cost of putting a similar number of SOLiDs into production,” Parkhill said.
But other users might come to different conclusions, he cautioned. “I don’t think people should take our choice as, necessarily, a comment on the relative qualities of each machine,” he said. “The reasons that we chose [Illumina] are very specific to our operations.”
Another possible factor in its decision is that Illumina’s UK headquarters — the former Solexa site — is a five-minute drive from the Sanger Institute, a proximity that could facilitate interactions between the two.
Parkhill acknowledged that the GA and the SOLiD platforms each have strengths and weaknesses for different applications, and vary in characteristics such as accuracy, sample requirements, or need for a reference sequence. But these differences were not large enough to call a winner.
“Any new group would have to look at the pros and cons themselves for the particular applications they wanted to use the machines for before they came to a decision, and I don’t necessarily think they should use our decision as a precedent,” he said.
Sanger scientists will use about half of the new instruments in externally funded projects, among them several cancer projects as well as a mouse project that aims to resequence about a dozen laboratory strains with different phenotypes.
The other half of the new machines will be devoted to internal projects, including expanding existing studies in the areas of human resequencing, cancer, and pathogen genomics, according to Parkhill. They will also help with “some continued moving of existing projects onto new technology,” he said.
In addition, Parkhill said, he and his colleagues found that an increasing number of Sanger faculty needed access to second-generation sequencing for applications like RNA sequencing, ChIP sequencing, and paired-end sequencing.
“We are finding a lot more of the faculty at the institute are taking on, or asking to use, the machines for new projects,” he said.
ABI: ‘Total’ Solutions
According to ABI, time might also have played a role in the Sanger’s decision to pass SOLiD over for its recent purchase. “They’ve had more hands-on experience with the Illumina technology and needed to achieve some major milestones quickly,” Jason Liu, senior director of business operations for SOLiD, said in an e-mail. “Their decision was driven primarily by timing, not by technology per se.”
Liu mentioned that ABI and cancer researchers at the Sanger Institute collaborated earlier this year to characterize structural variations in lung cancer and plan to submit their results for publication in the next few months (see In Sequence 5/13/2008).
Besides the Broad Institute, he said, other genome centers “are in the pipeline” for scaling up on SOLiD technology. ABI is focusing on “closing the gap with Illumina by putting strategic focus on the ‘total’ application solution,” he explained, for applications such as de novo sequencing, resequencing, or transcriptome sequencing.
On the bioinformatics front, besides a number of commercial and academic bioinformatics developers who have made their tools compatible with SOLiD, ABI has “commitments from several other developers” to do the same. ABI will help these and other efforts by “thoroughly documenting our color space algorithms,” Liu said.