Affymetrix's latest offering to researchers studying microRNA continues to stand alone in the marketplace.
A month after the firm launched catalog and custom genotyping arrays for the genome-wide evaluation of microRNA target sites, representatives for Agilent Technologies and Exiqon, two firms that compete against Affy in the miRNA array market, said they have no intention of launching a similar product. And while an Illumina representative said the firm plans to introduce arrays that include some similar content, a direct competitive offering is not planned.
Affy's Axiom miRNA Target Site Genotyping Arrays are different from existing products in that they survey DNA genomic variation involved in the regulatory machinery underlying miRNAs, while most other products to date have made the miRNAs and other non-coding RNAs available in an array format for expression profiling.
However, while Agilent and Exiqon said they do not plan to launch a product similar to Affy's, and Illumina said that next-generation sequencing is now its customers' preferred technology for such studies, that doesn't necessarily mean that demand is diminishing for array-based miRNA research tools. Instead, Exiqon and Agilent said they both expect to benefit from the availability of Affy's chips, and Illumina said it plans to make some of the same content available on future generations of its BeadChips.
"As far as I can see, the product is really intended to supplement [genome-wide association] or gene regulation studies and this is not a field Exiqon is currently working in," Lars Kongsbak, the Danish firm's CEO, told BioArray News this week. "But obviously Exiqon would be the natural choice to turn to for real-time-PCR-based validation of results obtained" on Affy's Axiom miRNA Target Site Genotyping Array, he added.
Exiqon was the first company to launch an array for profiling miRNA expression seven years ago. In following years, Invitrogen (now part of Life Technologies); Agilent Technologies; Affymetrix; Illumina; LC Sciences; Febit (now Comprehensive Biomarker Center); and Phalanx Biotech, among many others, jumped into the market, offering similar tools.
Affy was relatively late to the market, launching its first miRNA array in 2009, roughly three and a half years after the first miRNA chips were introduced (BAN 3/24/2009). Now, Affy's latest product offering does not seem to be creating a similar cascade of competing products.
"Our genomics team indicates that Affymetrix's new array addresses a different market and is looking at miRNAs at the DNA level for large studies," an Agilent spokesperson told BioArray News this week, "whereas Agilent miRNA microarrays are used by researchers looking at the RNA level, at mature miRNA profiles."
The way Affy's rivals portray its new miRNA product is not inaccurate, according to Michael Nemzek, vice president of strategic marketing at Affy. Nemzek told BioArray News that the firm decided to launch its Axiom miRNA Target Site Genotyping Arrays following discussions with "key opinion leaders" in cancer genomics and "other researchers studying variation in a variety of human diseases where the miRNA cascade is believed to play an important role."
According to the firm, the arrays interrogate 238,000 SNPs and insertion/deletions in genes for "all parts of the miRNA cascade," miRNA regulatory machinery, including miRNAs, their mRNA target sites, and silencing machinery. The firm also said the new chips, available in catalog and custom formats, complement some of its other products, such as its GeneChip miRNA 3.0 Array, its QuantiGene 2.0 miRNA Assay, and its ViewRNA in situ hybridization cell assay.
Though some industry observers believe that the Encyclopedia of DNA Elements, or ENCODE, consortium, which has assigned biochemical functions to around 80 percent of genome sequences, will hasten the transition from microarrays to sequencing for studying the role of microRNAs in complex diseases, Affy has argued that the ENCODE findings should bolster interest in its new chips. In fact, Nemzek said the company was moved to design the array based on the ENCODE findings.
"In light of the recent ENCODE results indicating a potential regulatory function for a large portion of the genome, we decided to put some of these regions on an Axiom array for use as a direct follow-up technique," Nemzek said. He said the resulting arrays provide researchers with the "opportunity to screen samples against an important class of variants relevant to such diseases, including cancer." He also claimed that 80 percent of the variants on Affy's new chips are not found on other widely used genotyping arrays.
Chistopher Streck, Illumina's marketing manager for RNA and epigenetics, said that the company's main applications for miRNA profiling these days are run on its next-generation sequencing platforms, rather than on arrays.
Streck told BioArray News this week that the firm discontinued its catalog miRNA arrays a few years ago, given the "tremendous amount of interest in sequencing-based microRNA research."
"Sequencing allows researchers to simultaneously conduct both discovery and profiling, detecting all known microRNAs, as well as any novel microRNAs," Streck said. And, "as microRNA sequencing requires the least amount of sequencing of any NGS application, the throughput and cost per sample is very low," he said.
That being said, Streck noted that the company has been reviewing ENCODE data to "identify variants across all known regulatory regions, not simply miRNA sites." For example, he said that sequencing has "illuminated promoter regions, sites with histone modifications, and transcription factor binding sites that are critical to regulatory control."'
Streck said that based on its review, Illumina plans to supplement its menu of BeadChips, such as its Human Methylation 450 array, and will expand its fixed content arrays using the new content. He added that the firm's customers are already interrogating the genomic targets included on Affy's array using its Nextera custom enrichment kits, as well as custom iSelect BeadChips.
While Affy continues to face competition from all these firms in the miRNA research tools market, Nemzek said that the company has so far experienced an "excellent reception" to the chips among cancer researchers. One customer is Stephen Gruber, director of the USC Norris Comprehensive Cancer Center at the University of Southern California. He said in a statement that studies performed at the center using the arrays are "showing promising results" and that the chips represent a "new opportunity to broadly interrogate an important class of variants relevant to cancer research." Gruber did not respond to an email seeking additional comment.
According to Nemzek, Affy sees its new chips as a follow-on tool for customers who have used its Axiom whole-genome genotyping arrays. "Virtually anyone who has done a GWAS study could have interest in running this array to supplement their studies," Nemzek said. "We have also found demand among researchers who have done exome sequencing and are interested in looking at important regions outside the exome to supplement their work without having to do additional costly sequencing experiments," he added.
Exiqon's Kongsbak said that his company also is seeing "steady interest" in its miRNA array products, despite the increased use of sequencing. "This may be of surprise to many, but perhaps the data analysis is just so much simpler than next-generation sequencing considering that the miRNome is relatively small and doable on arrays," he said. With regards to Affy's new chip, he offered that customers could use Exiqon's locked nucleic acid-based functional analysis tools for miRNA, such as its miRNA target-site blocker, to functionally validate the identified miRNA target sites on mRNA.
Like Exiqon and Affy, Agilent continues to see demand for its miRNA arrays, its spokesperson said, citing the "dynamic, ever-evolving miRBase database." The 19th version of the University of Manchester-hosted database, which was created in 2004, was released in August.
"The study of miRNAs and their gene regulation function continues to be a growing field," the spokesperson said. "In addition, with new miRNAs being discovered through NGS," she said, "there is a continued need to profile miRNAs on microarrays to determine signature expression patterns."
According to the spokesperson, Agilent will soon release a new SurePrint G3 8 by 60K microarray with probes designed to miRBase release 19. Still, that chip, once it becomes available, will be for profiling RNA, not DNA. And unless Illumina or some other company comes out with an offering to challenge Affy's, the vendor will continue to be able to refer to its products in promotional material as the "only commercially available high-density, genome-wide genotyping solution for microRNAs and their mRNA target sites."