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Higher-Density Chips and Array-Sequencer Pairings Will Define Array Market in 2008

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Several trends in the microarray market that emerged in 2007 hinted at the future of the sector, including across-the-board density upgrades by Affymetrix, Illumina, Agilent, and NimbleGen, as well as the pairing of arrays and next-generation sequencing technologies, which could portend future symbioses for the two platforms.
 
While the exits of ABI, GE, and Nanogen from the array market marked a year of maturation for the technology (see related story, this issue), the past 12 months also saw the debut of 1-million-plus-feature microarrays as well as the commercial launches of several next-generation sequencers — a technology platform that may prove to be more complementary to microarrays than competitive.
 
Affymetrix and Illumina both launched whole-genome genotyping arrays within weeks of each other in the second quarter. Affy’s 1.8-million feature SNP 6.0 Array debuted in May, while Illumina began shipping its Human 1M DNA Analysis BeadChip in early July. Both arrays combine SNPs with copy number variation content to meet the needs of researchers involved in genotyping studies (see BAN 5/29/2007, BAN 7/3/2007).

 

Steve Scherer, a senior scientist at the Hospital for Sick Children in Toronto, said that these arrays have ushered in a new period of “personalized genomics” that did not exist before.
 
“The new 1-million feature arrays from Affy and Illumina — with new ones coming from Agilent and NimbleGen — are really good products and for most of us in the field the threshold has now been crossed where we can do some really good genetics,” he wrote in an e-mail to BioArray News.
 
In terms of new high-density chips, NimbleGen has been in the process of upgrading its arrays to its 2.1-million feature HD2 format. HD2 arrays are already available for comparative genomic hybridization and chromatin-immunoprecipitation-on-chip analysis of eukaryotic organisms. Agilent, too, is planning to add 1.1-million feature arrays to its offering sometime this year (see BAN 12/4/2007).

 

While Affy and Illumina have been silent about plans for future density upgrades, some users believe it is inevitable that the two will again release higher-density chips.
 
“While I do not know Affymetrix's plans, the natural evolution of the genotyping platforms will be to even denser SNP coverage so that more ancient ancestral human populations can be adequately studied,” Dietrich Stephan, director and senior investigator in the neurogenomics division of the Translational Genomics Research Institute, told BioArray News in July (see BAN 7/31/2007).
 
However, neither Affy nor Illumina have discussed higher-density products for whole-genome genotyping studies. Affy, for example, has been urging customers to redesign their studies to more widely use the SNP 6.0, rather than promise greater coverage in a future product (see BAN 10/2/2007).

 

Chips and Sequencers
 
Another 2007 technology trend that is likely to impact the array market in 2008 is the launch of several next-generation sequencing instruments, including Illumina’s Genome Analyzer, ABI’s SOLiD System, and others.
 
Some, including Illumina CEO Jay Flatley, have touted the new “deep sequencers” as a new technology that will make analog expression arrays irrelevant. Flatley said he expects the expression market will grow in 2008, but mostly due to digital gene expression applications developed for use on the company’s Genome Analyzer.
 
“We had a researcher who we are very familiar with and who is a very fundamental person in this area demo the system and his statement after that demo was that DNA chips are very soon going to be dead, be passé,” Flatley said in June (see BAN 6/19/2007).

 

At the same time, Illumina’s growing technology catalog, which includes arrays, a next-generation sequencer, and a digital microbead-based instrument called the BeadXpress, illustrates the complementary nature of these technologies.
 
In November 2006, Flatley told BioArray News that Illumina views sequencing as a technology that will feed genotyping studies that also use array technology (see BAN 11/14/2006).

 


“Anyone making the conclusion that high-performance sequencing will replace arrays is a bit too overzealous at this point.”

“With sequencing, you discover the content, you understand the structure of the genome, and you discover things like SNPs and put them on a chip and do very high-throughput and fixed content genotyping,” he said at the time. “So it’s a discovery engine, if you will.”
 
Roche also sees arrays and sequencing as symbiotic technology tools. The Swiss firm made two interesting purchases this year by acquiring next-gen sequencing firm 454 Life Sciences for $154.9 million in May and NimbleGen for $272 million in August (see BAN 6/26/2007).

 

Lonnie Shoff, senior vice president of applied science and molecular diagnostics at Roche Diagnostics, told BioArray News in June that the firm sees sequencing and array technology as complementary in the marketplace.
 
“The combination of the two with ChIP-on-chip and sequencing was very attractive to us. And there are certainly some advantages to the arrays in the marketplace that we felt we could add to,” she said at the time.
 
In October, scientists using both technologies published articles in Nature Methods demonstrating how NimbleGen’s microarray technology can improve upon PCR for sample preparation in large-scale genome resequencing projects (see BAN 10/16/2007). 
 
This combination approach was given another boost last month when Prognosys Bioscience and Febit launched a Genome-to-Array service that first sequences microbial organisms using an Illumina Genome Analyzer and then makes the organism’s genome available in a more affordable array format through Febit (see BAN 9/25/2007).

 

Such deals, coupled with the comparatively high price tag attached to next-generation sequencing, have helped dispel the idea that next-gen sequencers will make array technology obsolete, according to Scherer.
 
“Since real affordable applications of next-generation sequencing are probably a few years off, I don't think arrays are going to disappear,” he told BioArray News.
 
Shawn Levy, director of the Microarray Shared Resource at Vanderbilt University, predicted that sequencing will play an increasing role in future studies but that the technology is “overhyped” at the moment. Sequencing “will not replace arrays and anyone making the conclusion that high-performance sequencing will replace arrays is a bit too overzealous at this point,” he wrote.
 
“There certainly are applications where this will shine but to say that it will completely replace arrays is simply ridiculous at this point, not too mention awfully expensive for the average user,” wrote Levy.
 
In another sign of scientists using both technologies together, Greg Crawford’s lab at Duke University’s Institute for Genome Sciences and Policy was awarded $6.5 million to identify and characterize regions of open chromatin using a cross-platform approach for the second phase of the National Human Genome Research Institute’s Encyclopedia of DNA Elements project (see BAN 10/16/2007).
 
Crawford told BioArray News at the time that Duke aims to “identify at high resolution all active gene regulatory elements in the human genome among cell types representative of most human tissues.”
 
His lab will seek to accomplish this goal by identifying regions of open chromatin with two independent and complementary methods: DNaseI hypersensitivity assays and formaldehyde-assisted isolation of regulatory elements. Crawford said this will be combined with chromatin immunoprecipitation for a small set of selected regulatory factors. 
 
”Each method will be coupled to two detection platforms: high-resolution whole-genome tiled arrays [from NimbleGen] and Illumina's sequencing-by-synthesis strategy,” Crawford said. “We believe that using this dual-platform approach allows for global validation.”

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