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Incyte Vies For Slice of High-Density Array Pie with New LifeArray Offerings

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Until recently, Incyte''s microarray division positioned itself firmly in the content and service business. The company provided patented and proprietary gene content from its databases for other companies to spot down on microarrays, and also performed in-house microarraying for researchers.

But in the past few months, as Incyte has revamped its overall strategy, the company''s microarray mission has changed. To take advantage of the increasing demand for prefabricated microarrays, the company began direct sales of its LifeArray microarrays at the beginning of the year, and has focused its service business on running experiments involving these arrays.

"For the last three or four years, we have been a microarray service business," said Chris Hopkins, senior scientist for Incyte''s microarray program. "Now we recognize the value of actually making the microarray. That''s really the focus of a lot of our business now."

In this effort, Incyte has been increasing the offerings in its microarray portfolio. The company currently offers a set of four human foundation LifeArrays, which it is increasing to six this quarter. Each LifeArray in this set has approximately 9,000 unique genes and ESTs, with 6,000 on average coming from Incyte''s database of proprietary sequences.

When LifeArrays five and six become available, the foundation set will offer a total of around 54,000 genes and ESTs, making it competitive with the Affymetrix U95 Human Genome set, which contains about 60,000 genes and ESTs from UniGene. Incyte also points out that its human foundation arrays have sequence only available in Incyte''s databases, which users can access through subscriptions; whereas Affymetrix only provides users with accession numbers for its probe sequences.

"We have over 100,000 gene bins, and close to half of these do not exist in the public domain," said Garrick Peters, an Incyte product representative, speaking to participants at a seminar on LifeArrays. The company compiles these gene bins from similar sequence in the public domain and its databases, and then picks the best representative from that bin when it selects sequence for microarrays, Peters said.

In addition to the human foundation set, Incyte also offers a human array based on the UniGene database; a human drug target array based on LifeSeq content; a UniGene-based mouse array; rat toxicology, rat central nervous system, and rat foundation arrays based on Incyte''s proprietary rat sequence; an Arabidopsis array from GenBank; a Candida albicans array; a Staphylococcus aureus array; as well as potato foundation and rice foundation arrays from PhytoSeq.

During the fourth quarter the company is planning to introduce a second mouse UniGene array, a second rat array, and a dog array based on portions of the beagle genome its scientists have sequenced; as well as a Saccharomyces cerevisiae and an additional Staphylococcus array.

For probes, Incyte has opted for longer cDNAs, rather than the short oligonucleotides.

Hopkins said the reason for this choice is that cDNAs offer superior performance. But another reason, which Incyte''s lawyers have noted in earlier interviews with BioArray News, is that cDNA arrays do not run as high a risk as oligonucleotide arrays of crossing into Affymetrix'' intellectual property domain.

In making the arrays, the company has instituted quality control measures at each stage of the process. There are quality control steps to monitor concentration of DNA in PCR, the quantity of RNA, to control for cross talk between spots, and to ensure that residual content has been removed from the printing pen. To monitor the process, Incyte has a barcoding procedure.

"We barcode everything," said Hopkins." We barcode plates and probes, and we barcode the people that work there."

The finished result, Hopkins said, has an increased sensitivity at the low level of expression. "With 95 percent confidence we can detect a 1.74-fold change."

Incyte touts this sensitivity as an advantage compared to other chips. "There''s a lot of interesting biology going on at the low expression level," said Hopkins.

But microarray analysis experts have called into question the validity of the fold change measurement itself, noting that the meaning of this measurement varies depending on issues such as type of sample and sample size.

"You can have a specific cutoff for fold change only if you believe the measurement error is constant across all of the genes regardless of whether you are studying humans or rats, said David Allison, a professor of biostatistics at the University of Alabama at Birmingham (see p.3 ) "I don''t think many people think this is the case."

Incyte also offers the statistic that 85 percent of the clones in its arrays serve as good discriminants of gene expression. "That''s pretty comparable to what oligo people are doing," Hopkins said.

The company''s R&D department is working on increasing the performance of the arrays and designing them as exon-specific to account for the phenomenon of alternative splicing, according to Hopkins.

Meanwhile, to promote its current technology Incyte is offering LifeArray seminars across the country.

"Our model is to lower the barriers to entry for the field," Hopkins said as he donned plastic gloves and prepared a Julia Child-like demonstration of a hybridization. "This technology is not the type that requires a core facility."

The company is currently offering offering 50 percent off services to people who attend the LifeArray seminars.

— MMJ