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ABI Adds Takara to SOLiD Service Provider Program as Current Partners Ramp Up Output

Applied Biosystems has added Japan’s Takara Bio to its SOLiD System Service Provider Program, and is planning several new features under the initiative, ABI officials said this week.
ABI launched the program in January as a way to familiarize genomic service shops with its second-generation sequencer and provide technical and marketing support for service providers who have adopted the SOLiD. Seven months on, the four firms who signed on as inaugural members [In Sequence 01-08-08] — Agencourt Bioscience, GATC Biotech, SeqWright, and Sistemas Genomicos — are at varying stages of rolling out their services on the platform, but all agreed that they are seeing strong interest in the SOLiD from their customers. 
Takara Bio, based in Shiga, is focused on three key areas: agricultural biotech; gene- and cell-based therapies; and sales of reagents, instruments, and services. The company operates a genomics services business called the Dragon Genomics Center in Yokkaichi.
Jason Liu, director of the SOLiD product line for ABI, said that while Takara Bio is the first Japanese service provider to join the program, it is not ABI’s first SOLiD customer in Japan. “We have multiple units placed in Japan,” he said. “We’re actually doing extremely well in the Japanese market.”
ABI spokeswoman Lauren Lum added that ABI is currently in discussions with additional international partners for the program, and that these agreements should be announced over the next several quarters.
Lum said that the company is also looking to add several new offerings to the initiative in the coming months, such as “application-specific training and educational seminars” for service providers and “other features as we expand the program.”
Liu said that feedback from ABI’s service partners has helped guide some of the firm’s product-development decisions — particularly around reagent kits for specific applications. For example, he noted that the SOLiD small RNA-expression kit, a barcoding tool for multiplexing small RNA-expression analysis that it launched on an early-access basis in July [In Sequence 07-29-08], should be of particular interest to service shops.  
The barcoding technology allows researchers to analyze up to 256 samples per run. This capability is important for service providers because of “the nature of their business,” Liu said. “They’ve got multiple samples for multiple users, and the capability to handle them in a multiplex fashion is very significant to improve their turnaround time, as well as to make their costs competitive.”
Liu said that the kit has been “extremely well received” under the early-access program and that the company expects to roll it out to the general market “in the very near future.” 
He added that the company is also “on the verge of launching an early-access kit for whole-transcriptome analysis.” Members of the SOLiD Service Provider Program and certain other ABI customers are entitled to these tools under the company’s early-access program.
The service provider program was initiated to support customers with a range of applications, including whole-genome sequencing, microbial and eukaryotic resequencing, gene expression, small-RNA discovery, chromatin immunoprecipitation, digital karyotyping, medical sequencing, and genotyping.
So far, ABI has focused on “two main buckets” of applications, Liu said: sequencing and tag-counting applications like gene expression.
“We’ve been working hand-in-hand with these service providers, figuring out what kinds of applications they are trying to tailor their business around and what their customers are interested in doing, and there are a lot of projects related to gene expression that SOLiD is very well suited for,” said Lum.
Several service providers agreed that gene expression is the primary non-sequencing application area for the SOLiD. SeqWright, which has been running its SOLiD “non-stop” since April, has so far conducted primarily resequencing, sequencing, and transcriptomes projects, according to Martin Storm, a scientist and project manager at the firm.
Spain’s Sistemas Genomicos, meantime, has not yet begun offering runs on its SOLiD to customers, but CSO Manuel Perez-Alonso said that resequencing and transcriptome analysis will be its first offerings for the service. The service is expected to launch in several months.
‘Not a Simple Machine’
Perez-Alonso said that Sistemas Genomicos received its SOLiD — its first next-generation sequencer — in mid-March, and that the system was “more or less operative” by the middle of May.
“The installation was really complex,” he said, noting that ABI provided an “army of technical scientists” to help the firm get up to speed on the platform.
Sistemas Genomicos is currently performing a series of internal validation studies on the instrument prior to offering services to customers. “When customers come, we say, ‘Wait a little bit, because this is not a simple machine or technology,” he said. 
Nevertheless, the initial data from the system seems promising. “Our first test has been resequencing of bacterial genomes. That’s working very well,” Perez-Alonso said. “Now we are doing it with fungal genomes. As soon as we end up with these tests, we will increase to mid-size genomes before doing a mammalian genome.”
Sistemas Genomicos intends to use the system for gene-expression analysis as well, “but we haven’t done any tests yet,” he said.
Perez-Alonso estimated that the company has done around eight to 10 runs so far and is averaging around three gigabases per run. “We believe that in the next few runs we will arrive at maybe six [gigabases],” he said. “But there are people who are getting 12, so I believe that will be growing.”

“When customers come, we say, ‘Wait a little bit because this is not a simple machine or technology.”

Liu said that some ABI customers are currently reporting runs of up to 15 gigabases and that the company’s scientists have attained more than 20 gigabases of mappable data per run in internal studies.
SeqWright, which has had a bit more experience with its system, is currently averaging around eight gigabases per run, Storm said, though he noted that the throughput is “dependent on the type of library we run.”
Genomic libraries are at the high end of the scale, he said, while transcriptomes and deep resequencing libraries generate “a little bit less data.”
Like Sistemas Genomicos, SeqWright hit a few speed bumps when installing the SOLiD. The system was installed in November 2007, but the firm didn’t perform its first run for customers until February. One reason for the delay was the holidays, but another factor was that “the installation of the SOLiD is definitely not just ‘plug it in and start running it,’” Storm said.
Storm said that he and another lab technician traveled to ABI’s headquarters in Foster City, Calif., for formal training, and then ABI staffers visited SeqWright’s facility in Houston, Texas, for on-site training, followed by weeks of installation runs and qualification runs on the instrument.
“Basically, it was a long and interrupted process to install it,” Storm said.
Despite the slow start, the SOLiD has “really exceeded expectations” at SeqWright, particularly since the system’s chemistry and software upgrade in May.
“Since the instrument upgrade, the data that has come out has been very, very good and the output has been very nice, and the data quality has been wonderful,” SeqWright CEO Fei Lu told In Sequence.
“Mainly, it was a change in emulsion chemistry and in the ligation chemistry on the instrument,” Storm said, “but it allowed us to produce far more data than we had previously — cleaner data.”
Perez-Alonso of Sistemas Genomics agreed that the upgrade made a “dramatic” performance difference. “Before the upgrade, the data were good but not extremely good,” he said. “Although it took some time to make the change from the initial version to the second version, now it’s really good.”
The biggest difference, Perez-Alonso said, is the reliability of the primary data. “The number of sequencing errors is reduced enormously,” he said.
Customer Curiosity
All four inaugural members of the SOLiD Service Provider Program reported a fair amount of customer interest in the platform.
Even GATC Biotech, which has since returned its SOLiD to ABI due to “changes” in its plans that resulted in the instrument “no longer fitting within its production workflow,” apparently did not do so out of lack of demand.
While GATC CEO Peter Pohl declined to elaborate on why GATC returned its instrument, he told In Sequence via e-mail that “customers were interested in the technology,” and that the company was fielding “many inquiries” from customers who had already had their projects sequenced with the Illumina Genome Analyzer and planned to compare this data with data from the SOLiD.
“Most of these customers inquired about paired-ends for resequencing projects (mainly human),” Pohl said.
Stone said that SeqWright is also seeing “a lot of interest” in the SOLiD. “I take at least a couple calls or e-mails a day, I would say, of people who are interested,” he said. “We have a lot of interest, but obviously, it’s one of those things that is not suitable for every customer.”
Indeed, some providers indicated that managing customer expectations is a big part of the next-gen sequencing services business as new instruments come online. Lynn Doucette-Stamm, vice president of business development at Agencourt Bioscience, a subsidiary of Beckman Coulter, told reporters at a conference earlier this month that the firm, which has two SOLiD instruments in production, often gets specific requests to run jobs on the platform, which it sometimes must decline.
Speaking during a press luncheon at the Drug Discovery and Development of Innovative Therapeutics conference in Boston earlier this month, Doucette-Stamm said that when Agencourt gets these queries, it typically asks customers exactly what they want out of an experiment. It turns out, she said, that the SOLiD “is not always the correct choice for what they want to do.”
Doucette-Stamm declined to provide further comment for this article.  
SeqWright, which offers SOLiD and 454 sequencing, follows a similar approach, Stone said. “The 454 is much better suited for certain applications, and the SOLiD is much better suited for certain applications. I just steer our customers toward the technology that would make them happy,” he said.
Data Analysis is Top Challenge
Both SeqWright and Sistemas Genomicos cited bioinformatics as one of their biggest challenges with the SOLiD so far.
“The greatest challenge, at least from my standpoint, has been the data analysis,” said SeqWright’s Stone. “It generates so much data. And our customers are not accustomed to this type of data. We kind of have to hold their hands … [they] need help understanding the data, tools that we develop for them, and things like that.”
Currently, he said, SeqWright is using ABI’s software tools for primary analysis, matching, alignment, and other tasks, “but to visualize the data, we mostly use tools that we have developed and tweaked in-house,” he said.
Perez-Alonso agreed that data analysis “will probably be the main challenge” for the SOLiD and other next-generation sequencers, especially as service firms scale up to the point of sequencing complete human genomes, “which is something that I believe will become routine within five or 10 years for a company like ours.”
The amount of information from the system is “huge,” he said, “but how we will simplify it and extract the most relevant information for a medical doctor, and of course for a [patient] …the data analysis and processing … will be really a challenge.”
Sistemas Genomicos is using ABI’s software and is also collaborating with two academic bioinformatics groups to develop “specific software that will be able to do other things that the software from ABI is not able to do,” Perez-Alonso said, though he declined to elaborate.
ABI, for its part, is aware of the informatics challenges that the SOLiD presents for service providers and other customers. Liu, the product line director, said that while the priorities and requirements of its different customers sometimes vary — service providers are looking to turn around the maximum number of samples in a short time in order to remain profitable, for example, while academic customers might be more interested in novel applications — the one issue that everyone can agree on is informatics.
“I would say that everybody sees bioinformatics as a huge challenge,” he said. “This is true not just for service providers, it’s true for everybody.”
The key problem, he said, is that second-generation systems are “being judged by past bioinformatics and IT infrastructure,” in which the three-gigabase human genome “was considered the ultimate test.”
Now, he said, “one SOLiD run generates 6, 7x coverage of a human genome. This is really a paradigm shift and in many ways the whole industry is scrambling to understand what is the best way to cope with so much data.”
Liu cited ABI’s SOLiD Software Development Community Program, which it expanded last month to include four new commercial partners and five new internally developed open source software tools, as its key strategy for addressing this informatics challenge.
Liu noted that the software program is not limited to commercial partners, and that the firm is working “closely with academic researchers” to help make SOLiD analysis tools available through the Software Development Community website.  
Liu added that ABI’s decision to release its SOLiD software under an open source license demonstrates “significant progress” in its transformation from a closed-platform Sanger sequencing shop. Through the Software Development Community site, “bioinformatics and IT gurus can download the source code and play around and see how we developed the data analysis software.”
The goal, he said, is to “encourage the whole bioinformatics community to develop something even better and tailored for their specific application.”
— Julia Karow contributed to this article.

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