Illumina this week introduced a new family of "cost-efficient" genotyping arrays geared toward biobanks, genome centers, and core labs.
Several of the company's customers welcomed the chips' debut, saying that the new arrays will support ongoing efforts to discover and characterize common and low-frequency variants in large sample cohorts.
And Affymetrix, Illumina's main competitor in the genotyping array market, pledged this week to soon launch arrays for large screening studies.
San Diego-based Illumina already provides a menu of high-density Omni whole-genome genotyping arrays, but these chips, which have a minimum of 730,000 markers, are not optimal for some customers engaged in larger projects, according to the firm. Illumina said in a statement that it introduced the new Core-branded chips, which start at 260,000 markers, to tap this demand for "affordable, large-scale genotyping."
Jennifer Stone, marketing manager at Illumina, explained the decision to launch the new family of arrays, pointing to a "need to interrogate not only exonic regions but also provide genome-wide coverage at low cost for large-sample studies looking for well-powered [genome-wide association studies] in addition to [copy number variation] analysis."
Stone told BioArray News this week that Illumina has seen "increasing interest in population-level or consortium-type studies, which can include ... hundreds of thousands of samples."
Illumina hasn't disclosed pricing for the new chips, but is offering them at a reduced price through an early-access program that ends Dec. 31.
There are two new arrays. The HumanCore BeadChip contains 240,000 genome-wide tag SNPs found across "diverse world populations" as well 20,000 additional "high value markers," including insertion/deletions and updated exome focused content. The chip also has the capacity to include up to 200,000 semi-custom markers, according to the firm.
The HumanCoreExome BeadChip, meantime, includes the 240,000 tagSNPs found on the HumanCore BeadChip, plus all 240,000 markers from Illumina's HumanExome BeadChip, the updated exome-focused content, and the capacity to include up to 20,000 semi-custom markers. Illumina introduced the HumanExome BeadChip last year and sales of the array have exceeded the company's expectations (BAN 5/15/2012).
Both of the new Core arrays are based on Illumina's Infinium assay and can be run using the firm's iScan, HiScan, or HiScanSQ systems. The company suggested the chips could be used for common variant genome-wide association studies, large-scale copy number variant detection, mtDNA studies and ancestry tracking, among other applications.
Christian Henry, Illumina's general manager of genomic solutions, said in a statement that the new chips were "specifically designed to make genotyping accessible to a wider range of researchers and laboratories," and that they "combine affordability and high-throughput sample processing."
Mark McCarthy, a professor at the University of Oxford, told BioArray News that the HumanCoreExome BeadChip in particular will be "valuable for research utilizing large sample studies" and that the availability of arrays consisting of genome-wide tag SNPs, exome markers, and the ability to add custom content "will drive the next wave of association discovery for SNPs and CNVs."
McCarthy said he was part of the discussion group that defined the "broad remit" of the array design. Stone said that researchers from other institutions, including the University of Michigan, the Broad Institute, and Massachusetts General Hospital, also contributed to the design of the arrays.
While array-driven association studies have been described by some as yesterday's experiment, McCarthy said that there are "many valuable samples out there that have not been [studed via] GWAS, particularly [in] some of the large biobanks." He acknowledged that array costs have fallen in recent years, but said that by the time the costs had decreased sufficiently for these biobanks to genotype their samples, "some of the enthusiasm to fund GWAS work had started to abate." That situation changed to some extent with the availability of the HumanExome BeadChip last year, and "many of these cohorts are now being typed on the first version of the exome array," said McCarthy. He speculated that the new HumanCoreExome BeadChip will "logically supersede the existing exome array" because of its content and lower price, which McCarthy said is about $15 less per sample.
"The ability to combine a scaffold GWAS with exome variant coverage, at a pricepoint of around $60, should enable many other interesting cohorts to contribute to ongoing efforts to discover and characterise common and low frequency variants," said McCarthy.
Illumina does not disclose pricing for its genotyping arrays on its website, but some centers that offer the arrays as a service do. The Johns Hopkins University SNP Center, for instance, charges $82 per sample for the HumanExome BeadChip, while the Yale Center for Genome Analysis charges $75 per sample for the same array. At the other end of the spectrum, JHU charges $725 per sample genotyped on the 4.3 million-marker Omni5, while Yale charges $800. Prices vary depending on sample volume.
Though most of his sample collections have already been evaluated through GWAS or exome studies, McCarthy said that his lab will use the HumanCoreExome BeadChip as its "stock chip" for characterizing genetic variation in some ongoing studies, including potentially some large multi-ethnic projects investigating type 2 diabetes risk, including up to 50,000 samples.
McCarthy also suggested that the array could be used for "sanity checking" of large cohorts to "fingerprint" and "establish structure" in samples prior to sequencing. "It will be a logical partner for RNA-seq analyses," he said.
Illumina launched its first whole-genome genotyping array based on the Infinium assay, the 100,000-marker Human-1 Genotyping BeadChip, in 2005 and over the past seven years has launched incrementally higher-density chips for association studies, culminating in last year's rollout of the 4.3 million-marker HumanOmni5 and HumanOmni5Exome BeadChips, the latter of which includes 4.3 million tag SNPs and 240,000 exon markers and spurred orders to process more than 1.3 million samples in its first six months of availability, making it the company's best array debut to date (BAN 5/15/2012).
But, according to Anthony Brookes, a professor in the department of genetics at the University of Leicester in the UK, the genomics research field "is now maturing beyond the need for only standard whole-genome genotyping chips."
Brookes, whose center offers Infinium genotyping as a service, told BioArray News that there are two "directions" shaping the array market, one that "entails support for even larger and lower cost studies" and another that calls for "added flexibility of content."
Still, he cautioned that while Illumina seems to be addressing both of these needs "in one go" with its new Core family of BeadChips, it "may or may not work" in the marketplace.
"It might be wise to additionally separate these two objectives, and provide suitable chips for each," Brookes suggested. "A third needed direction, related to the added flexibility of content, would be much lower capacity arrays that still provide low cost per SNP, per sample data points," he added. "This would support fine mapping studies in large sample numbers, implying the need to test tens to hundreds of variants," said Brookes.
According to Brookes, "cheap and convenient solutions" for such projects are "lacking." He speculated that next-generation sequencing "with wet lab or even bioinformatics-based genome partitioning will eventually fill this gap." However, he pointed out that "even smaller content solutions will surely be needed for many targeted diagnostics applications, and here arrays might yet win the day over NGS."
Despite Brookes' reservations, Tomas Axelsson, head of SciLifeLab's genotyping facility in Uppsala, Sweden, said that Illumina's new chips meet a clear demand in his county.
"Given the vast number of DNA samples that are stored in Swedish biobanks, if Illumina and us as service providers can find ways to reach these customers, there is potentially a large market" for the arrays, Axelsson told BioArray News this week.
Michael Nemzek, vice president of strategic marketing at Affy, said the Santa Clara, Calif.-based firm also recognizes the demand for such tools. Nemzek told BioArray News this week that the "genotyping of larger sample cohorts to achieve maximum power in association studies represents a trend that human genetic researchers have begun to take" and that microarrays offer the "most cost effective" approach toward achieving that objective.
According to Nemzek, Affy has been collaborating with the same investigators that aided in the design of Illumina's Core arrays to develop an Axiom microarray offering for genotyping and screening studies on large sample numbers "as typically conducted by biobanks, genome centers, and core labs."
Though the company has not officially launched the chip, it is taking orders for it, with anticipated delivery within the next four to six weeks.
According to Nemzek, the array has coverage of more than 650,000 variants, is "fully customizable," allows users to impute millions of SNPs from an "intelligently designed genome-wide marker grid" with coverage across major populations using an algorithm licensed from the University of Oxford, and provides access to functionally-relevant content with coding and loss of function SNPs and indels discovered in recent exome sequencing studies.