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Febit Sets Roadmap for HybSelect Upgrades to Exploit 'Wide Open' Target-Enrichment Market

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As part of an effort to stake its claim in the nascent target-enrichment market, Febit plans to make over the next few quarters a series of upgrades to its HybSelect application that will enable it to make higher-density arrays in a multiplexed format.

Additionally, the Heidelberg, Germany-based biotechnology firm is developing with partners a whole-exome biochip that will contain "biomedically relevant" protein-encoding exons. The chip will be geared towards oncology researchers, but will also contain content for those studying neurological disorders and other diseases.

Febit has also inked an OEM deal with UK software developer InforSense to provide additional informatics support for its HybSelect customers.

Scientists from Febit discussed both the coming HybSelect upgrades and the new whole-exome biochip at Select Biosciences' Advances in Microarray Technology meeting, held in Stockholm, Sweden, last week.

Peer Stähler, Febit's chief scientific officer, told BioArray News in an interview this week that the company now has a "complete roadmap" for HybSelect including "molecular biological improvements" and "physical platform improvements" that will materialize in coming quarters.

Febit launched HybSelect in February. The application is used to capture targeted sequences for use with second-generation sequencing platforms. According to the firm, oligonucleotides are synthesized within the eight channels of a Febit Geniom biochip and then used as capture probes for the targeted genomic DNA loci within a sample. The fragmented genomic DNA is then hybridized to the biochip, washed, and eluted. After elution, the selected DNA can be used for sequencing (see BAN 2/17/2009).

HybSelect can either be run on Febit's Geniom instrument, a microarray production facility that enables users to synthesize and run their own arrays; or on the firm's RT-Analyzer, which supports the analysis of arrays prepared by Febit.

The application competes against offerings from rivals like Agilent Technologies, which is co-marketing its SureSelect target enrichment app with Illumina; Roche NimbleGen, which co-markets its sequence capture arrays with Roche 454 Life Sciences; Raindance Technologies; LC Sciences; and a number of other players (see BAN 3/3/2009).

The biochip that Febit currently uses for HybSelect provides 1.25 megabases of data per array, meaning that each biochip can offer 10 megabases of data for the user. Febit, though, is planning to raise its array density to offer a 32 megabase biochip in a second version of the chip due in the fourth quarter, followed by a 240 megabase biochip by the first quarter of 2010.

Stähler said that the main benefit of the higher-density arrays will be the ability to cover each data point with several probes, which will increase the reliability and statistical power of results obtained using HybSelect.

The density increase will also provide "good scalability in terms of multiplexing versus density," he said, meaning that the company did not have to sacrifice chip real estate to make room for the additional content.

In addition to the density upgrade, Febit is also planning to make other changes in HybSelect over the next few quarters. Stähler said that the company is optimizing a "whole toolbox" of methods for generating a fragment library out of a sample, rather than using "standard methods of target enrichment."

Because HybSelect has mostly been used with the Illumina Genome Analyzer II, Febit had been using Illumina's protocol for generating libraries. Now, said Stähler, the company will have a number of options from which to choose. Febit also plans to introduce protocols for using HybSelect with the Life Technologies' SOLiD platform, sold by its Applied Biosystems division, over the next few months. Febit has been working with the University of Kiel in Germany to optimize its HybSelect protocol for the SOLiD.

Finally, there are the changes coming from the sequencer vendors themselves. As BioArray News sister publication In Sequence reported in February, both Illumina and ABI expect to increase the output of their instruments to around 100 gigabases per run by the end of the year through a combination of hardware, software, consumables, and reagent improvements, lowering the cost of sequencing and potentially expanding the market.

"Those upgrades will play into our hands a lot, because that's all going to be capacity that we can use," said Stähler of the impending upgrades. Still, he urged customers not to wait until next year to take advantage of new versions of HybSelect.

"These technologies are not trivial," Stähler said. With second-generation sequencers, "you need a year to be really in a productive modus. If you need this to be routine in 2010, you cannot wait until 2010 to start doing this," he said. "I think it's a wise step to get in this game early."

In regards to the competition, Stähler said that the target-enrichment market is "wide open," and that the field is so new that there is no obvious front-runner. "There is no clear winner or number one choice right now," he said. This will all be sorted out in 12 months. Then there will be one or two competitive players who have 80 percent market share and the rest are deemed exotic," he said.

"For us, the market is exploding," he added. "We get more inquiries than we know what to do with."

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Whole Exome

As part of HybSelect application development, Febit has also been creating catalog arrays to serve the needs of certain customer segments. With this approach, array design is less burdensome because the company can offer a theme array that only requires some modifications to meet its client's requirements, according to Stähler.

The first such tool to come out of this process is the firm's 2 megabase Cancer Exon Biochip. This chip, which became available this spring, contains probes for approximately 580 genes and is available as a catalog array or together with custom content.

Stähler said that Febit plans to add to the content of the Cancer Exon Biochip in coming months with the overall aim of launching a full protein-coding exon set early next year. Febit has not decided what content will make it onto the whole-exome biochip, but said that its custom projects "indicate a strong interest in disease-associated loci."

Of all communities Febit is serving, Stähler noted that those studying oncology are the "most enthusiastic" about using second-gen sequencing, and therefore would be the target customers for such an array. The company also has partners doing Alzheimer's disease studies, for instance, and is interested in integrated findings from genome-wide association studies into the new chip.

Febit is also working with scientists at Harvard University, the Translational Genomics Research Institute, the Max Plank Institutes, the University of Kiel, and Prognosys Biosciences to develop content, Stähler said.

"We are considering several focus areas" for the whole-exome chip, he said. "We haven't decided on all disease loci, but we are assessing content together with partners, to see what makes the most sense for their needs."

Informatics and Inforsense

Febit is also investing resources into its bioinformatics support to be able to handle queries from HybSelect customers. Stähler said that Febit has nearly a dozen bioinformaticians, both in Heidelberg and at its US office near Boston. "It's pretty challenging as the data coming out of these projects is enormous," he said. "Even the hardware needs to be upgraded to handle the data."

This month Febit inked an original equipment manufacturing deal with London-based InforSense to integrate components of its data analysis software tools into the software it provides for use with HybSelect. The new software package will give Febit users access to InforSense’s VisualSense, which offers interactive web-based visualization of data, as well as workflow capabilities engineered by the British firm.

Stähler said that HybSelect requires an informatics platform with the "ability to handle massive amounts of data, which can then be boiled down and presented in manageable size pieces to our end-users." He called the deal with InforSense part of an effort by Febit to "get technology on board that we don't have to develop ourselves." Stähler did not elaborate on terms of the deal.

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