NEW ORLEANS — The promise of financial gain resulting from pairing microarray technology with DNA methylation research has lured NimbleGen, Agilent, and Genpathway into the epigenetic market. Now Illumina is preparing to enter the nascent field by planning to launch a methylation assay by the first quarter of 2007, according to a company official.
Carsten Rosenow, Illumina’s marketing manager for DNA analysis solutions, told BioArray News that two papers in Genome Research have been published describing the firm’s methylation assay.
Rosenow, speaking during the American Society of Human Genetics meeting, held here last week, also said there “is a high interest among Illumina customers [for us] to commercialize our methylation” technology.
According to Rosenow, Illumina’s methylation assay, called the GoldenGate Methylation BeadArray platform, is an extension of the firm’s existing GoldenGate assay technology that is based on high-throughput genotyping of bisulfite-converted genomic DNA. The assay pairs an Illumina BeadChip with a methylation cancer panel, which enables it to interrogate up to 1,536 CpG sites from about 800 genes per sample, Rosenow said.
This week Karen Possemato, associate director of marketing at Illumina, told BioArray News in an e-mail that after launching its methylation assay the company plans to make available custom genotyping panels for methylation studies.
In her e-mail, Possemato added that the company is preparing to include a methylation module in its BeadStudio analysis software that will “allow researchers to compare methylation status and gene expression levels,” among other features.
Why All This Sudden Interest?
Illumina‘s entry coincides with other new companies' in the methylation market. Earlier this month, for instance, Genpathway launched a methylation service using Affymetrix tiling arrays. Last month Agilent Technologies launched its Human 244K CpG island microarrays for epigenetic research. And NimbleGen said it plans to introduce a methylation service this quarter.
Two other firms with methylation arrays include Epigenomics and Orion Genomics, however both companies have decided to keep their arrays as in-house research tools only (see BAN 6/27/2006
“This is a whole existing area of cancer research,” Rosenow explained. “Methylation and copy number variation both come out of the cancer community, which is one of the most well-funded research areas. That’s probably why you see people getting a gleam in their eye every time they talk about methylation.”
In terms of approach, Illumina is unique so far in the marketplace. While NimbleGen and Agilent are using gene expression assays, Illumina has chosen to use its genotyping assay instead, Rosenow said.
“This will allow the user to identify the base that is methylated,” he said. Other companies “can tell you the region but they can’t tell you what base is methylated.”
Emile Nuwaysir, vice president of business development at NimbleGen, said that Rosenow is correct that NimbleGen’s arrays do not identify which base is methylated. But he also claimed that Illumina’s method “is not practical as a genome-wide screen.”
“The method Illumina employs relies on bisulfite treatment of DNA followed by site-specific SNP assays,” Nuwaysir said. “This is useful for mapping DNA methylation in single-base locations within the genome, but is not practical as a genome-wide screen.”
Rosenow could not be reached for further comment.
While Illumina’s approach may differ from its rivals, all of these companies are seeing dollar signs when it comes to using methylation to locate epigenetic markers that may help diagnose cancer, diabetes, and age-related diseases.
“The diagnostics potential is certainly very appealing,” said Rosenow last week. His sentiments were echoed by Mary Warren, chief scientific officer at Genpathway, which launched its Methylated DNA IP-on-Chip assay using Affymetrix tiling arrays earlier this month (see BAN 10/3/2006).
“Methylated DNA ... provides a promising approach for diagnostic tests that help in choosing the best therapies and monitoring response to treatment,” Warren told BioArray News in an e-mail this week.
“Methylation and copy number variation both come out of the cancer community, which is one of the most well-funded research areas.”
According to Warren, Genpathway is offering its clients “completely analyzed results,” including the locations of all methylated DNA regions and their relationships to genes and other sites, such as CpG islands, using the most current genome annotation.
“These results also provide comparisons between the methylated DNA regions from different samples so that clients can see easily the differences in DNA methylation between different cells or tissues,” Warren wrote. “The results can then be compared with other data such as gene expression data.”
In that sense, Affy’s tiling arrays may be used in a similar manner to Illumina’s genotyping assay. “Methylated DNA results are more similar to genotyping because they give information directly about the genome as opposed to RNA profiling, which gives information about the product of gene expression,” she wrote.
Still, while comparing Agilent, NimbleGen, Genpathway, and Illumina’s offering may make some sense at this stage of the game, some experts in the field say that the real rival technology for an assay like Illumina’s is PCR.
“They don't really compete with each other,” said Mahendra Rao, referring to the platforms made by NimbleGen, Genpathway, and Illumina. Rao, who left the National Institute of Aging to become vice president of research in Invitrogen’s stem cells and regenerative medicine unit earlier this year, added that the gene-expression assays “need to be correlated with DNA methylation of the specific gene locus.”
“There are, however, methylation-specific PCR and other strategies that compete with DNA-based strategies and sequencing-based strategies,” Rao added.
If that is the case, Illumina might find itself butting heads with Applied Biosystems in the methylation market. ABI last week introduced a reagent kit and analysis software for methylation-specific PCR. The firm claims its methylSEQr Bisulfate Conversion Kit and its Methyl Primer Express Software will “simplify applications such as bisulfate sequencing and fragment analysis in DNA methylation experiments.”