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In 'Mature' Expression Array Market, Vendors See Future in New Formats and Genomes

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By Justin Petrone

Depending on who you ask, the market for gene-expression microarrays is either flat or growing slowly. Some large vendors consider the space, now more than a decade old, to have become commoditized: It’s more about taking market share from rivals than winning new customers.

Still, companies say that there are new trends underway in the marketplace that could revive demand for gene-expression chips.

Representatives for Affymetrix, Agilent Technologies, Illumina, and Roche NimbleGen told BioArray News in recent interviews that the market is being driven by a number of factors. These include the ability to screen multiple samples per array, cost per sample, the availability of up-to-date content, and scalable assays.

Additionally, vendors say they have benefited from the adoption of second-generation sequencing platforms, though in different ways. As new genomes become available, particularly for animals and crops of interest to the agricultural biotechnology community, reps for Affy, Agilent, and Roche said that customers are demanding access to new whole-genome gene-expression arrays.

According to Illumina, which also sells a sequencing platform, the broad gene-expression market is experiencing a "renaissance" as new customers use its Genome Analyzer for transcriptomes sequencing. Currently, the firm's RNA-seq application accounts for a quarter of all runs on the system, and the company expects to convert more array users to sequencing over time.

Fighting for Share

In the expression array market, Affymetrix has always been the company to beat. Founded in 1991, Affy launched its first commercial GeneChip system in 1994, at a time when none of its present competitors even existed. This head start was one factor that allowed Affy to gain and retain a majority share of the expression array market.

Affy currently offers a variety of options for those interested in doing gene expression. The firm sells 3' IVT arrays, tiling arrays, exon-level arrays, gene-level arrays, and microRNA arrays. The firm's chips also come in different formats: both its older GeneChip cartridges, which run on its GC Scanner 3000 instrument; and in its high-throughput Array Plates, which were launched in 2008 for expression and run on the GeneTitan system. Affy expects to launch a lower-throughput, benchtop system called GeneAtlas for Array Plates early next year.

Rebecca Brandes, associate director of product marketing for RNA applications at Affy, said that Affy's cartridge-based Human Genome U133 Plus 2.0 Array continues to be the firm's "most widely used product," followed by its Exon and Gene 1.0 ST Arrays, both of which are experiencing "sustained growth."

Brandes said the Santa Clara, Calif.-based firm's different arrays and formats serve different kinds of customers. While its Exon 1.0 ST Arrays have "found high adoption in academic research," Gene 1.0 ST Arrays have "found their place not only in discovery but in drug rescue programs," and the GeneTitan Instrument and Array Plates are being adopted in academic core labs and by pharmaceutical companies.

In Affy's view, the market for gene-expression arrays "continues to grow in part [because of] the accessibility of array technology and products, as well as the move from discovery projects to screening large numbers of samples." Brandes said that Affy is "aggressively defending" its share of the gene expression array market, which "remains the largest," by launching new products.

Specifically, she said that Affy will launch U133 and U219 Array Strips with the GeneAtlas next year, followed by gene-level arrays and some updated model organisms later in the year. "We will continue to develop our arrays, assays, and analysis to fit the needs of the evolving expression market."

While Affy looks to stay on top, other companies are looking to chip away at its market share by getting its customers to switch to their platforms.

"We continue to see growth in gene expression, but the overall market for arrays is not necessarily growing," said Alicia Burt, director of microarray marketing at Agilent. "I would say that right now it's more of a market share game" involving competitors like Affymetrix, Illumina, and Roche, she said.

Burt told BioArray News last month that the exit of other players like Applied Biosystems and GE Healthcare from the expression microarray market, plus the adoption of commercial platforms by researchers that previously used home-made arrays, has provided Agilent with opportunities to grow its expression business.

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Agilent currently offers whole-genome gene-expression arrays for human, mouse, and rat in multi-pack formats that allow users to run one, two, four, or eight samples per slide. Agilent also offers catalog arrays of nearly 30 other model organisms. Through the company's eArray online tool, customers can also design their own whole-genome arrays.

Having offered expression arrays for nearly a decade, Agilent now plans to launch its first SurePrint G3 gene-expression arrays by March 2010. The new, million-probe G3 expression arrays will offer users the ability to run eight samples on eight, 60,000-probe arrays per slide, Burt said. Agilent currently offers gene-expression arrays that enable users to run eight samples on eight arrays of 15,000 probes.

"The demand is certainly there. There is pressure for us to deliver the 8x60K arrays," said Burt of the new expression chips. According to Burt, the "biggest drivers" for expression array adoption at the moment are content, performance, and price per sample.

Tsetska Takova, director of arrays and reagents at Roche NimbleGen, also cited cost, content, and multiplexing capabilities as factors that lead customers to adopt Roche's platform. NimbleGen offers catalog whole-genome, gene-expression arrays for around a dozen model eukaryotic organisms including human, mouse and rat, as well as custom-designed arrays. The company's chips are available in three different formats: one array by 385,000-feature, four-array by 72,000-feature, and 12-array by 135,000-feature.

"Recently, the trend in the gene expression microarray market has been towards multiplex solutions that maximize array content while still providing a cost-effective solution to lower the cost per sample and increase the sample throughput," Takova told BioArray News. "Array content, performance and price per sample, and workflow are the key factors for the gene expression array market."

Shawn Baker, market manager for expression and regulation at Illumina, had a similar view of the market for gene-expression arrays.

"If you talk about the expression array market, then I would agree that it's pretty flat," Baker told BioArray News. "We are still seeing growth and presumably that's coming at the expense of competitors. We are seeing some decent growth, but the market itself is not growing. It's a mature market; people that have access to technology are using these arrays."

Illumina currently offers whole-genome BeadArrays for human, mouse, and rat studies. Baker said that the firm's Human HT-12 array has the strongest demand of any of Illumina's expression array products.

Though the company is eager to win new customers for its Genome Analyzer, Baker said there is "still a life" for arrays. "We anticipate that product being around a few years and it definitely will include new content updates," Baker said of the HT-12.

In the past, Illumina has openly encouraged customers of other firms to switch to its platform, and Baker said that it is still part of the San Diego company's strategy. But the distinction between the platforms goes beyond just content or multiplexing capability, he said.

"All the main platforms do a pretty good job," Baker said of the content on rival expression chips. "Given that bar of performance has been met, people are focusing on other things. They are pushing for high-throughput systems and costs as low as possible."

Baker said that Proctor & Gamble recently acquired an Illumina system and switched a "significant portion of their work over to our arrays" from a rival platform. "The quality and price made us an option for them."

Academics are "definitely the majority" of Illumina's expression array customers, Baker said. Still, he said Illumina is "seeing a lot of pharma and pharma-like companies switching over to our arrays because of cost and throughput issues," but noted that "these same people are also sticking their toe in the water in terms of sequencing."

The Sequencing Factor

As market manager for expression and regulation, Baker said arrays are only part of the equation for Illumina's strategy. As the company offers both arrays and sequencing, it can offer potential customers interested in expression profiling access not only to a lower-cost, scalable assay, but an entirely different technology platform.

"There's the broader view, where you are a researcher who just has a question and you can use arrays or sequencing," Baker said of the expression market. "I think that sequencing is starting to cause a renaissance. It is giving researchers a new view of the transcriptome they have never had before. Even splice arrays are nothing compared to what you can see with a simple RNA-seq experiment," he said.

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According to Baker, Illumina is "planning for a switchover time from arrays to sequencing." He said that, right now, there are "two major directions people can go. If they are interested in high-throughput, low cost, then arrays will give them that solution. At the other end of the spectrum, there are people who are interested in a detailed view of the transcriptome, looking at less well-characterized species, and there sequencing is the way to go."

Illumina does not break out revenues for expression sales, be it from arrays or sequencing, but Baker said the sequencing side of the business is "definitely growing" and noted that 25 percent of applications run on the Genome Analyzer are RNA-seq. According to Baker, RNA-seq is directly competitive with the exon or tiling expression arrays sold by competitors.

"It's a process," Baker said of the move from arrays to sequencing. "This will take time, and it will not be a uniform switch. We think people will switch from more complicated arrays, like exon and tiling arrays, and then going down the chain. The less expensive an array is, the longer it will be around."

One might think that such words would intimidate other array vendors, but Affy, Agilent, and Roche all say that their array businesses, particularly their custom array offerings, are being buoyed — not threatened — by the adoption of second-gen sequencers.

"We can quickly and cost-effectively add newly sequenced genomes and develop whole-genome or custom focused array content," said Roche's Takova. "Next-gen sequencing does and will continue to provide content for gene expression array design. This is especially true for the biotechnology field. We are seeing a lot of demand for gene expression arrays based on the latest genome builds of crop plants and farm animals, such as pig, salmon, bovine, and grape and expect this trend to continue," she added.

Affy's Brandes similarly reported growth in the firm's MyGeneChip Custom Array Program. "As the databases are flooded by sequencing data, Affymetrix and its customers are taking advantage of this," Brandes said. "It is a very efficient way to verify findings from next-generation sequencing."

According to Brandes, Affy in particular is seeing a "large increase in custom arrays coming from large agriculture and biotechnology consortia to take advantage of sequencing." She added that food safety is also a growing area for Affymetrix custom arrays.

And despite the growing adoption of sequencers, Brandes said that arrays are still, in general, the easiest and most cost effective way to "understand phenotypically what is occurring due to biological events, such as a SNP or copy number variation."

Unlike Affy, Agilent, and Roche, Illumina has decided not to offer custom gene-expression arrays or expand its catalog of model organism expression arrays. "We built one for human, mouse, and rat. We decided the markets weren't big enough to justify arrays for other species," Baker said.

Now that the company has the GA, that limitation does not exist anymore for the company, he said. "There are people doing work on all sorts of niche species. You are seeing a broadening of our customer base in that sense," he said. "The advantage for them is that they don't have to wait for an array to be made," he added. "What is nice for us about sequencing is that it runs on any sample."

However, Illumina doesn't envision the discontinuation of its gene expression array platform. "The company absolutely wants to maintain its diversity," Baker said. "It's why we still have the array platform. It will be a significant transition to convert every assay out there over to sequencing," he said. "The truth is that may never happen," he added. "For some applications, arrays will always exist."

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