In a year when the word "sequencing" was on everyone's lips, microarray-based applications advanced steadily into routine clinical use.
During 2010, arrays became the standard of care for detecting constitutional abnormalities and researchers prepared to set guidelines for using arrays in clinical cancer cytogenetics.
At the same time, array manufacturers concentrated their efforts over the past 12 months on developing new products for genome-wide association studies with the hope that renewed growth in the market will blossom in 2011. As the first GWAS projects performed on a new generation of higher-density, custom-built genotyping chips are now wrapping up, firms anticipate that the success of these studies will translate into adoption of their new products.
Indeed, if there were two words that defined the array market in 2010, they were "cytogenetics" and "GWAS." Half of the top 10 most widely read BioArray News stories last year concerned the cyto-testing market, while three focused on the use of chips in association studies.
Rounding out the top 10 stories of 2010, listed below, was a piece on the use of arrays in direct-to-consumer genetics, as well as a story on potential M&A activity by one the space's biggest players, Affymetrix.
The most widely read story last year was Illumina's announcement in January that it aimed to submit a cytogenetics-themed package to the US Food and Drug Administration (BAN 1/26/2010). Greg Heath, Illumina's senior vice president and general manager of diagnostics, said the company will submit the package as part of its preliminary investigational device exception, or pre-IDE, process.
As part of that process, test makers can send analytical or clinical protocols to the FDA for review and comment before proceeding with studies and can discuss possible regulatory pathways.
Illumina was not alone in engaging the FDA with regards to obtaining clearance for array products that can be used in cytogenetics. During the year Agilent Technologies, Affymetrix, and Roche NimbleGen all discussed their plans to eventually submit packages to the agency (BAN 7/20/2010).
At the same time, the FDA has not yet settled on what criteria its review process will entail. The FDA's Office of In Vitro Diagnostic Device Evaluation and Safety hosted a meeting in June with test providers, array manufacturers, and other experts to address that issue (BAN 7/6/2010).
The FDA's attempt to regulate the use of arrays in cytogenetics comes at a time when the technology is becoming more accepted as the platform of choice for diagnosing genetic abnormalities.
The second most-read story of the year was the American College of Medical Genetics' recommendation in September that chromosomal microarrays become geneticists' first-line postnatal test (BAN 9/28/2010).
For David Ledbetter, chief scientific officer and executive vice president of Geisinger Health System, the new ACMG guidelines are the "first official statement that we have replaced the karyotype with a new test, the cytogenetic array."
As head of the International Standards for Cytogenomic Arrays consortium, Ledbetter has helped steer an effort aimed at setting standards for arrays to help diagnose genetic abnormalities.
In May, ISCA published a statement in the American Journal of Human Genetics that recommended using arrays as "first-tier" tests to assess individuals with unexplained developmental delay and intellectual disability, autism spectrum disorder, or multiple congenital anomalies (BAN 5/18/2010). BAN's coverage of the recommendation was the eighth most-read story of the year.
The success of ISCA in helping to set guidelines for the use of arrays in constitutional cytogenetics has motivated others to set standards for the use of arrays in cancer cytogenetics. The Cancer Cytogenomics Microarray Consortium this year intends to carry out a multicenter, multi-platform validation study to demonstrate that the new technology is reliable and reproducible enough for clinical use in cancer diagnostics (BAN 11/30/2010). Coverage of CCMC's study was BioArray News' seventh most-read story of the year.
Overall, the cytogenetics market was arguably the most dynamic segment for arrays last year, leading firms beyond the traditional array makers, like PerkinElmer, to jump in. PerkinElmer spent $90 million to acquire Signature Genomics in April (BAN 4/20/2010).
Waiting for a Second Wave
While the market for cytogenetic arrays surged ahead in 2010, the genome-wide association market began to climb out of a 2009 lull with the release of next-generation genotyping offerings from main suppliers Affy and Illumina. Still, the large, array-based GWAS blueprint came under criticism as some researchers argued that smaller, next-generation sequencing-based studies were a more cost-effective way to identify the genetic bases of human diseases.
Both West Coast array vendors made major product announcements during the year. Illumina in July launched the Omni2.5-Quad, a four-sample BeadChip that contains 2.5 million markers per sample and includes rare variant content from sources such as the 1000 Genomes Project. The Omni2.5 became Illumina's bestselling chip in the third quarter, and array sales were up year-over-year during every quarter of 2010 (BAN 11/2/2010).
Affy, meantime, continued to roll out the Axiom genotyping offering it launched late in 2009, complementing generic whole-genome arrays with chips designed for studying specific populations. The Santa Clara, Calif.-based firm has already made genome-wide arrays available for studying European and East Asian populations on its next-generation Axiom genotyping platform.
A Chinese population-specific custom product, called the Axiom Chinese myDesign Genotyping Array, will be launched this year (BAN 11/9/2010).
Though genotyping array sales revived in 2010, company officials say the market is not yet where it should be. Illumina Chief Financial Officer Christian Henry said last month that it was "important for early projects" that rely on the new arrays to "show success, which will then drive the next wave of GWAS" (BAN 12/7/2010).
Henry predicted that some data from early studies should become available early this year. "GWAS will continue to grow [in 2011]; how fast will be dependent on how these early programs wrap up," he said.
As vendors ramped up to position themselves for a second wave of GWAS, some researchers warned that the approach would eventually hit a wall, and recommended a different way forward. Researchers at Duke University Medical Center argued early in the year that performing whole-genome sequencing on a smaller number of individuals, as opposed to performing larger genome-wide association studies on genotyping arrays, will help to identify the rare variants that cause common diseases (BAN 2/2/2010).
While they acknowledged that genome-wide association studies have been effective in finding common variants associated with human disease, the Duke researchers cautioned in a PLoS Biology paper that rare, undetected variants may underlie those associations. Finding the missing heritability of diseases, therefore, will require a smaller, sequencing-based approach, rather than using a GWAS to locate a particular genomic region of interest, and then using targeted sequencing to locate the rare variants, they argued.
The argument did not sway manufacturers, however. Illumina CEO Jay Flatley said in January that while there is enthusiasm for Illumina's sequencing instruments, the company believes that arrays are currently "faster," "cheaper," and "more accurate" than existing next-generation sequencers for GWAS (BAN 1/19/2010). Stories on the Duke paper and Flatley's statements were the sixth and fifth most-read stories, respectively, in BioArray News in 2010.
The Top 10 Most Read BioArray News Stories of 2010
3. Critiques of BU's Longevity Study Raise Questions about GWAS Methods (July 13, 2010)
4. Affy, Illumina Arrays Remain Platforms of Choice for Consumer Genomics Firms (Feb. 23, 2010)
5. Illumina CEO Says Next Round of GWAS Will Be Done on Arrays, Not Sequencers (Jan. 19, 2010)
6. Duke University Medical Center Researchers Warn 'GWAS Will Hit a Wall' (Feb. 2, 2010)
10. Affymetrix Eyeing Tuck-In Acquisitions to Bolster Downstream Market Presence (May 11, 2010)
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