When it comes to the choice of using arrays or next-generation sequencing to discover copy number variants, the optimal approach is to combine the two platforms, according to Daniel Siu, vice president of Axeq Technologies.
The Rockville, Md.-based firm, a division of the Korean genomic-services company Macrogen, last week began offering a high-resolution CNV-detection service based on whole-genome sequencing and array-based comparative genomic hybridization.
In a statement, the company said that despite both technologies' individual shortcomings — array CGH's false positives and negatives and next-gen whole-genome sequencing's inherent inability to capture all CNVs — combining them "offers the most comprehensive estimates of personal CNVs to date."
This week, Siu told BioArray News that by offering both methods in the same service Axeq can overcome their individual faults.
"Current paired-end or mate-pair sequencing misses about 50 percent of CNVs," Siu said. "Plus, you cannot get breakpoint determination with single-base precision."
Siu argued that "combining the two orthogonal technologies allows the detection of a significant portion of the remaining 50 percent of the CNVs not efficiently captured by sequencing alone."
Moreover, the resolution of sequencing data helps to remove many false positives and negatives from CNV candidates from CGH data, he said. To accomplish this, Axeq relies on bioinformatics capabilities developed by parent Macrogen.
Over the past decade, the Seoul-based service provider, which maintains subsidiaries in the US, the Netherlands, and Japan, has "accumulated sufficient informatics tools to achieve this objective," said Siu.
Axeq began operating in January. The firm was initially founded to sell sequencing services worldwide via offices in Rockville, Amsterdam, Tokyo, and Seoul. Though Axeq shares some resources with Macrogen, Siu said that the companies are becoming "more and more independent" of each other: Axeq focuses on sequencing and genotyping while Macrogen pursues a number of different business opportunities.
"Think of Macrogen as Toyota, and Axeq as Lexus," Siu said.
Axeq's new CNV-discovery service is aimed at "researchers who require high-resolution variant analysis for discovery research, especially those who study common complex diseases," according to Siu. The service is run on two platforms: an Illumina HiSeq 2000 sequencing instrument and Agilent Technologies-manufactured CGH arrays.
The chip on which the service is based, dubbed the Axeq CNV microarray, contains 180,000 features. It was developed and validated by Axeq and scientists at the Genome Medicine Institute at Seoul National University.
The list of CNVs was selected from an initial 24-million-feature, whole-genome CGH array that was used to survey variants in 20 Caucasian, 20 West African, and 30 Asian individuals.
Part of the study was performed using arrays made by Roche NimbleGen (BAN 7/7/2009), which later went on to design its own CNV-themed arrays based partially on that content (BAN 9/29/2009).
Siu said that Axeq's chip contains more than 5,000 CNVs discovered by the Genome Medicine Institute at Seoul National University, 4,000 CNVs discovered by the Wellcome Trust Sanger Institute in the UK, and coverage of an additional 1,200 genes of interest.
Siu claimed that Axeq can offer reference-free genotyping with the array.
"Unlike conventional CGH approaches, our probe analysis has been converted from relative genotypes to absolute genotypes via multiple rounds of validations with whole-genome sequencing," he said.
Because the firm doesn't rely on reference sequencing to make calls, the "numbers of false positives and false negatives have been dramatically reduced," he said, without elaborating.
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In addition to receiving sequencing and genotyping data, Axeq's clients will obtain lists of "immediately usable data, including carefully mapped SNPs, indels, CNVs, and other structural variations with extensive annotations, so they can rapidly progress to discovering causative variants," Siu said.
'Not a Low-Cost Leader'
Axeq has no shortage of genotyping- and sequencing-service rivals. Depending on geography, the firm faces off against a number of firms, both pure-play service providers and companies that offer customized services as one of several business areas.
In the US, Axeq's rivals range from Research Triangle Park, NC-based Expression Analysis to Aliso Viejo, Calif.-based Ambry Genetics, to name two. In Europe, potential competitors could be services shops, like Charleroi, Belgium-based DNAVision, as well as firms that offer custom genomic services with catalog arrays and other offerings, like Oxford Gene Technology. In Asia, Axeq competes with Beijing-based CapitalBio and Shenzhen, China-based BGI, among many others.
Siu said that Axeq faces off against rivals by providing a quality service as opposed to a lower price point.
"We are not a low-cost leader," Siu said. Rather, "we are a premium brand delivering very high-quality data with original technologies developed by our in-house specialists."
That said, Siu does not believe that combining array CGH and sequencing in one service will make Axeq's offering cost prohibitive.
"Macrogen/Axeq is one of the largest CGH facilities in the world'," Siu said. "We manage cost very effectively," noting that pricing for the new service could range from $5,000 to $12,000 per sample depending on project scale and complexity.
All projects include "whole-genome sequencing, CGH genotyping, and massive bioinformatics," Siu said.
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