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Febit, Launching HybSelect, Enters Increasingly Competitive Sequence-Capture Array Market


German microarray company Febit entered an increasingly crowded market this week by launching its HybSelect microarray DNA-capture product for second-generation sequencing.

HybSelect is available as a product and service that uses either a catalog or custom arrays. The product initially targets users of the Illumina Genome Analyzer who want to sequence up to 9.5 megabases of genomic DNA.

The company said that within the next year, it plans to increase the target size to 30 megabases, release additional catalog arrays, and optimize HybSelect for other second-generation sequencing platforms.

Febit's new product enters the sequence-capture market closely behind a number of potential rival sequence-selection or targeted-enrichment methods made by companies such as Roche NimbleGen, Agilent Technologies, and RainDance Technologies (see In Sequence 2/24/2009 here and here).

But the firm, which is headquartered in Heidelberg and has a US site in Lexington, Mass., believes there is room for more players.

"The market for sequence capture is brand-new and just starting to unfold," Febit Chief Scientific Officer Peer Stähler told In Sequence earlier this month. "There is a huge demand [in] the market," enough so "it can easily feed more than one company," he said.

"I think the market will start to settle a little in one or two years from now, but right now it's just very early," Stähler added.

HybSelect makes use of Febit's microfluidic Geniom Biochips, which can hold up to eight samples, and the firm's Geniom RT Analyzer, which processes and reads the arrays.

The biochips carry up to 120,000 probes, 15,000 in each of eight separate channels, with a probe length of up to 60 nucleotides. At launch, Febit will offer a single catalog array with exons from about 600 cancer genes, or 2 megabases of total DNA. Also available will be custom arrays covering up to 9.5 megabases of genomic DNA. Customers can request content from any sequenced organism.

The method "typically" requires a microgram of DNA, Stähler said, though Febit is starting to explore whole-genome amplification and expects "soon [to] see nanogram numbers."

Stähler declined to disclose pricing information for the arrays or the Geniom RT Analyzer, but said that the Geniom RT Analyzer costs "less than" a second-generation sequencer, which he said typically runs at $500,000.

Over the next year, he said, Febit plans to increase the capacity of the arrays to more than 30 megabases of target DNA per biochip, as well as launch additional custom arrays. Increasing the target size to 30 megabases per channel of a biochip is "an option we consider," according to Stähler.

HybSelect will be available both as a service and as a product. For the service, users submit DNA and their regions of interest, and Febit returns sequencing data generated on the Illumina GA. Customers using the product prepare DNA in their own labs using HybSelect arrays and the Geniom RT Analyzer. Febit offers existing Geniom One microarray customers "favored conditions" for purchasing an RT Analyzer, Stähler said.

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Febit chose to offer HybSelect initially for use with the Illumina Genome Analyzer "because that [platform] has the biggest user community," according to Stähler. By mid-2009, the firm plans to add a protocol for the Applied Biosystems SOLiD, and will "probably" also support the 454 GS FLX in the future.

Febit has no co-marketing agreements with any sequencing company in place at the moment, said Stähler.

He said one advantage of HybSelect is that the Geniom RT Analyzer is highly automated and only requires half an hour of hands-on time as part of a 2-day HybSelect run.

In an internal project, Febit used HybSelect to target 1,000 500-base regions, each with a centrally located SNP that were chosen from a 1.5-megabase region from a HapMap sample.

Running two samples on a single biochip, company researchers were able to cover about 90 percent of the SNP positions, with at least 20-fold coverage with Illumina sequence reads, and 99-percent of SNPs called from these data were concordant with the reference sample. The scientists also correctly called about 98 percent of heterozygous SNPs "with no evidence of allelic bias," according to Febit's website.

The average depth of coverage in the experiment was almost 500-fold, which Stähler said could enable users to run several barcoded, or indexed, samples on the same array.

"It's a prerequisite to have a high depth of coverage to be able to conduct indexing, and we show that we have that," he explained.

In addition, researchers could trade depth of sequence coverage for more different capture probes, thus expanding the target size.

'Cautiously Optimistic'

As part of its early-access program for HybSelect, Febit has recently signed on groups at the National Institutes of Health and at Johns Hopkins University, though initially on a service basis, Stähler said.

It also recently delivered a Geniom RT Analyzer to the CEA/Centre National de Génotypage in Evry, France, where researchers plan to use HybSelect as part of READNA, an EU-sponsored research consortium to develop new sequencing technologies (see In Sequence 3/3/2009)

And over the last few months, Febit has tested HybSelect with San Diego-based Prognosys Biosciences, a Febit partner (see In Sequence 12/18/2007); the German Cancer Research Center in Heidelberg; and the Translational Genomics Research Institute in Phoenix.

At TGen, investigator Matt Huentelman has used HybSelect as an early-access customer in order to sequence a 45-kilobase disease-associated region of the genome.

Before starting to use HybSelect, he had worked with Febit's Geniom One array technology for about two years for other applications, including customized copy number and mRNA-profiling studies, and his lab recently acquired an RT Analyzer.

"I am cautiously optimistic that this platform is going to have a lot of utility for investigators with a focused hypothesis" that involves a region of the genome that is too large for long-range PCR, Huentelman told In Sequence earlier this month.

He said his lab's aim is for 50 percent of all mappable reads derived from a HybSelect experiment to be from the selected target. Febit is "not exactly there yet, but they are absolutely in the region where I think it's going to be positive in the future," Huentelman said, adding:"The enrichment is absolutely in the right ballpark to be useful."

Another potential advantage of HybSelect is that "you can very quickly do iterations to improve upon your probe design," and that customers can design a separate Febit array for copy-number analysis to assess whether the HybSelect enrichment has worked. However, his lab has not done the latter yet, Huentelman added.

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Though his group is quite invested in the Febit platform, Huentelman said "we have to be open-minded about other approaches" depending on the application. "Each one has pros and cons. I think there is not a clear front runner yet."

HybSelect joins several microarray-based target-capture products for second-gen sequencing.

Roche NimbleGen earlier this year introduced it Sequence Capture 2.1 Human Exome microarrays, which cover nearly all human exons, or 30 megabases of target sequence, after starting to offer capture arrays for up to 5 megabases of target DNA last year. The company's protocols are optimized for sequencing the captured DNA with the 454 Life Sciences platform.

Later this year, Agilent plans to introduce capture arrays as well, which are currently being tested by early-access customers. These arrays will initially be optimized for use with the Illumina Genome Analyzer, with the Applied Biosystems SOLiD to follow (see In Sequence 2/24/2009).

Also, Houston-based LC Sciences last month launched an array-based custom target enrichment service that is based on the firm's µParaflo biochip technology (see In Sequence's sister publication, BioArray News, 3/3/2009)

Febit will present HybSelect at Cambridge Healthtech Institute's Next-Generation Sequencing conference in San Diego this week, and in a webinar on March 25 that will also include results from its catalog cancer exon biochip.