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Array Firms Scramble to Make New Chips As Sanger’s MicroRNA Database Expands

Within hours of the twelfth version of the miRBase database of published miRNA sequences and annotation going online Sept. 1, a host of array companies began pledging to update their miRNA offerings to reflect the most up-to-date content available.
The database, which is hosted by the Wellcome Trust Sanger Institute and the University of Manchester in the UK, typically undergoes upgrades once or twice each year on an unscheduled basis.
MiRBase 12.0 has 8,619 entries, 25 percent more than version 11.0, which was released in April. Therefore, companies that offer miRNA chips, like Febit, Agilent Technologies, Illumina, Invitrogen, and Exiqon, see a market advantage in being able to rapidly provide the newest miRNA content.
Febit, a Heidelberg, Germany-based biotech that sells arrays for use on its Geniom platform, began advertising that it had updated its arrays to reflect the latest miRBase content hours after version 12.0 went online.
Chief Scientific Officer Peer Stähler told BioArray News this week that the company can move from database release to a ready biochip design within 12 hours. “Febit software calculates the appropriate oligonucleotides very fast; the array design is followed by synthesis of the Geniom biochip and Febit’s quality control,” he said.
“Within 48 hours” Febit’s biochip is ready for use in its miRNA services, which means that “if a customer sends his samples right with the release of the new miRBase version to Febit, Febit can start right away with the analysis,” Stähler said.
According to Stähler, Febit’s ability to quickly design probes and synthesize new chips using its Geniom platform has given it an advantage in the quickly moving microRNA market, where content is continuously revised and expanded. It’s an advantage that Febit does not necessarily have against larger array firms in other, more mature markets, such as gene expression, where Affymetrix, Agilent, and Illumina tend to dominate.
“MiRNA is Febit’s business,” said Stähler. “Due to our extremely short production time, we don’t need to know in advance” about a release. “Looking at the latest two versions of [MiRBase], Febit had the chip with the new version ready before Sanger sent out its newsletter that the new version is out,” he said.
Stähler added that, because Febit’s chips are often synthesized for custom projects, the firm can integrate predicted but unpublished non-coding RNAs on to chips on demand. “The timely production of customized biochips is the entry for scientists to high-speed genomics,” he said.
Committed to MiRNA
Providing miRNA analysis tools may be Febit’s business, but it is also the business of a number of array companies, all of whom have launched tools, services, or both to meet the growing demand for miRNA research since Invitrogen and Exiqon became the first to enter the market in 2005 (see BAN 11/16/2005, BAN 11/23/2005).
Since that time, firms like CombiMatrix, Febit, Agilent Technologies, Illumina, Asuragen, and Oxford Gene Technology have set their sights on serving the miRNA community. This week, several companies told BioArray News that the latest version of miRBase warrants new products that will become available over the next two months.
According to Chris Streck, product manager of gene expression and regulation at Illumina, the company will release the next version of its miRNA expression-profiling panel in early October, a year after the firm stepped into the miRNA array market (see BAN 9/18/2007).
Streck told BioArray News this week that both Illumina’s12-sample BeadChip and 96-sample array matrix will include content from miRBase 12.0, in addition to “novel content identified by Illumina scientists using our sequencing technology, and content identified in literature but not yet included in miRBase.”

“In a field that moves as fast as microRNAs, everything is inevitably more or less out-of-date.”

Streck said that Illumina has a “rapid process in place” for continuously designing and updating its assay panels without interrupting customer workflow. He also said customers use the firm’s second-generation sequencing technology to discover new miRNAs and profile samples with known content.
“With this approach, there is no lag time between the identification of new targets and implementing them to a commercially available panel,” he said. Streck added that it is important for customers to have “the most up-to-date content to investigate the implications of miRNA in their model or disease,” but that “data quality is paramount.” He claimed the company has a “robust design pipeline and testing procedure” to ensure that it can accurately identify the targets in its panel. 
At Agilent, the next arrays to include content from miRBase 12.0 will most likely launch in November. Sangita Parikh, Agilent’s miRNA product manager, told BioArray News this week that it generally takes about two months for the company to make updated miRNA arrays available following a miRBase release, but that customers benefit from the firm’s quality-control procedures.
“We could produce the arrays faster, but Agilent performs extensive wet validation on new microarrays,” she said. “Customers tell us that they value the additional confidence that this provides.”
Parikh noted that while the number of new sequences in miRBase increased by 25 percent, the number of new sequences for human, by far the most widely studied organism, only rose by 22 entries, or less than 1 percent.
Deluged by Data
There is no official schedule for miRBase upgrades, but since the resource went online in December 2002, releases have tended to appear every six months. According to Sam Griffiths-Jones, a research fellow in the life sciences faculty at the University of Manchester who has overseen the database since its formation, miRBase may soon take on new funding, additional personnel, and, perhaps, a more fixed schedule.
Griffiths-Jones told BioArray News this week that miRBase has never had any formal funding beyond general research funds from Manchester, and, earlier, the Sanger Institute, where Griffiths-Jones held a research position.
“I really want to explore ways in which I can increase miRBase’s resources and increase the number of people working on miRBase, so that we can really develop the database in directions it should be going,” he said.
Currently, Griffiths-Jones single-handedly handles the upgrades, so new releases are dependent upon his personal schedule.
“It may come as some surprise to people that there is one person behind miRBase,” Griffiths-Jones said. “I don’t envisage that any more than me plus two others is required to do a really good job of microarray database provision.” Griffiths-Jones added that he is in talks with academic and business partners that could help to further develop miRBase as a resource.
Part of that development would be committing to a fixed schedule of releases. At the same time, because the number of miRNAs continues to expand, Griffiths-Jones warned that researchers will always be somewhat behind the curve in conducting their studies.
“There are a load of advantages to that research schedule, but the flipside is that miRNA discovery is so rampant that a fixed release is somewhat out of date very quickly. Part of the challenge is keeping up with the deluge of data,” Griffiths-Jones said. “I guess ideally people always want to use the most up-to-date data available, but in a field that moves as fast as microRNAs, everything is inevitably more or less out of date.”
The vendors themselves are unsure of how large miRBase will eventually grow. Febit’s Stähler predicted that the number of known regulating RNAs will “grow exponentially with the knowledge of its functions and impact in genomics,” while Illumina’s Streck said researchers are “finding more and more novel miRNA,” though most of the new miRNAs are expressed at low levels.
Agilent’s Parikh declined to speculate on how large subsequent releases of miRBase could be, but stressed that the firm will “concentrate on providing up-to-date analytical tools, no matter how big the database grows.”

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