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Affy Bets Its New European Cancer Research Alliance Will Expand ChIP-on-Chip Business

Affymetrix is betting that an alliance it recently formed with around 30 European cancer labs will help it grow its chromatin immunoprecipitation (ChIP)-on-chip business and give it an edge over rivals Agilent Technologies and NimbleGen Systems.
As part of the so-called Collaborations in Cancer Research Program, Affy will partially fund selected research projects that demonstrate clinical utility. The company will also help participants obtain a variety of Affy tools, and will train them and provide forums for investigators to exchange knowledge and share best practices.
The alliance is expected to add researchers in North America and Japan later this year, the company said. Affy will not have any IP rights to discoveries that come out of the alliance, it added.
According to Affy, the studies selected for the CCRP will use a number of different applications on the Affymetrix platform, including gene expression, copy number analysis, and, in particular, ChIP-on-chip.
The company has to date played in the ChIP-on-chip space directly and through service providers like Genpathway, but those efforts have often been eclipsed by its activity in the fiercely competitive whole-genome genotyping and gene expression markets, as well as its forays into clinical diagnostics.
Affymetrix and some researchers in the CCRP agree that the collaboration is an opportunity for the company to make headway in the still-nascent ChIP-on-chip market and they believe its platform and sales and marketing muscle will help grow the sector in tandem with efforts from rivals such as NimbleGen and Agilent.
The timing is noteworthy: Affy has embarked on this effort as Agilent introduces higher-density chips, and as NimbleGen, which filed for an initial public offering with the US Securities and Exchange Commission last month, gears up to serve the European market directly after years of relying on distributors (see BAN 3/20/2007). 
Ruby Gadelrab, a senior market-development manager at Affymetrix, told BioArray News in an e-mail last week that five labs in the new program will be using Affymetrix's ChIP-on-chip protocols with the company's whole-genome tiling arrays, including groups at Charite-Universitatsmedizin Berlin Institute of Pathology in Germany, the University of Cambridge in the UK, Aarhus University Hospital in Denmark, the Spanish National Cancer Center, and the Naples OncoGenomic Center in Italy.
In addition, Gadelrab wrote that Affy will push the application by establishing web forums and setting up workshops to discuss its approach to ChIP-on-chip.
Affy also held its first European ChIP-on-chip scientific meeting in Dublin, Ireland, last month and a US equivalent is planned for September, according to Gadelrab. Among its latest ChIP users are European labs working on disease areas such as breast cancer and lymphoma.
CCRP User Apps
Manel Esteller, the director of the cancer epigenetics lab at the Spanish National Cancer Center in Madrid and a CCRP member, said he decided to use Affy's ChIP assay because of the firm’s track record in other applications like gene expression, as well as its bioinformatics capabilities.
"There are many companies trying to establish the best platform for ChIP-on-chip analysis," Esteller told BioArray News this week. "Affymetrix has an excellent track record for expression arrays and I think for them it is now the right time to attempt the next level — ChIP-on-chip. So we are starting this collaboration to really double-check the platform that they have," he said.
Esteller's lab is focused on cancer epigenetics, and in particular he studies DNA methylation and histone modifications in cancer cells. He said that he is using "many different approaches" for ChIP-based studies, and that his lab has used arrays from NimbleGen and Agilent in the past with varying success.
"As with all technologies, these platforms have advantages and some caveats," he said. "I think that the most important part is the bioinformatic treatment of the data. I think that Affymetrix has put in a good effort to try and make the data generated in these level approaches easier to understand for the researcher."
He added that while labs like his and others in the program are using ChIP-on-chip for cancer research, the technology could be "fruitful for all areas of biology," including more complicated areas like neurodegenerative disease research. "I think that many times, cancer research is just the first line of late-breaking research," Esteller said.
"Many technologies start in cancer and then they move to other areas. I am sure that if you do ChIP-on-chip on brain samples, they would be very nice studies and I am sure they will be done in the future," he added.
According to Affy, Ashok Venkitaraman, a professor in the department of oncology and the Medical Research Council Cancer Cell Unit at the University of Cambridge, will use ChIP to explore the roles of the BRCA1 and BRCA2 genes, which were among the first genes to be linked to a high-penetrance risk of developing early-onset cancer. In addition, Michael Hummel, a group leader at the Charite-Universitatsmedizin Berlin Institute of Pathology, will use Affy's promoter tiling arrays to study transcription factor binding in lymphoma.
Other researchers in the program using ChIP-on-chip could not be reached for comment.
Market Expansion
Affy's push into the ChIP-on-chip market is likely to spill into similar projects as alliances in North America and Japan are announced later this year. But the reenergized effort to sell the application actually comes two years after NimbleGen Systems and Agilent Technologies led the array field by rolling out their ChIP-on-chip applications (see BAN 2/22/2005, BAN 1/5/2005).
In comparison, Affy launched its whole-genome tiling arrays at the end of 2005, but did not begin marketing the arrays for ChIP-on-chip analysis until recently.

"Affymetrix has an excellent track record for expression arrays and I think for them it is now the right time to attempt the next level — ChIP-on-chip. So we are starting this collaboration to really double-check the platform that they have."

Now that Affy has stepped into the ChIP-on-chip stage, it is looking to capitalize on its ability to offer arrays at densities that rival Agilent's with sales and support muscle that could challenge NimbleGen, especially in foreign markets, where the smaller company has just begun building a direct sales and support presence.
"Affymetrix has the unique advantage of content," Gadelrab wrote. "With up to 6.4 million features on each array, we enable researchers to look at entire genomes at a very high resolution on a very low number of arrays."
The genome-wide approach to ChIP studies has been endorsed by service providers like Genpathway, which offers an assay based on Affy's tiling arrays, and Aviva Systems Biology, which offers its internally developed genome-wide ChIP service (see BAN 1/30/2007).
At the same time, rivals like Agilent are relying on their printing technology and custom array services to bolster their play in the ChIP market. For instance, Rini Mukherjee Saxena, Agilent's ChIP-on-chip product manager, told BioArray News in an e-mail last week that because "researchers doing ChIP-on-chip tend to do custom experiments," the firm's SurePrint ink-jet fabrication method is well-suited for meeting market needs.
Additionally, Saxena wrote that Agilent's ChIP offering had experienced "tremendous growth" and has become a "key component of Agilent's genomics business" over the past two years due to growing interest from cancer biology and endocrinology researchers.
In her e-mail, Gadelrab agreed that cancer is the gateway for expanded ChIP-on-chip use. "This application should be very important for epigenetic regulation of gene-expression studies, and will hopefully lead to breakthroughs in cancer classification, diagnostics, and therapeutics," she wrote.
Still, while it is convenient to frame the ChIP market as a choice between several platforms, researchers will likely follow a similar path as the Spanish National Cancer Center's Esteller, who has used most of the major platforms available on the market.
For example, Bing Ren, an assistant professor of cellular and molecular medicine at the University of San Diego, told BioArray News last week in an e-mail that he has been using both the NimbleGen and Affymetrix platforms due to their differing strengths.
The "NimbleGen platform offers good signal-to-noise ratios and higher reproducibility at individual probe level, [while the] Affy platform offers higher probe density and lower price," Ren explained.
Citing its pending registration with the SEC, NimbleGen declined to comment for this article.

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