Baylor College of Medicine’s Chromosomal Microarray Analysis service will now use an oligonucleotide microarray manufactured by Agilent Technologies instead of the bacterial artificial chromosome arrays it used in the past, according to a Baylor official.
Additionally, the institution has partnered with Athena Diagnostics to outsource the business side of the CMA service, a decision that could give BCM a lift in the testing market.
Both decisions could have repercussions in the array comparative genomic hybridization-testing market, where some consider oligo arrays to be the most accurate and others criticize them for being too noisy and unreliable for diagnostic purposes.
Art Beaudet, chair of Baylor's department of molecular and human genetics, which runs the university’s Medical Genetics Lab and offers CMA, told BioArray News in an e-mail this week that the lab has decided to scrap its older platform for an oligo platform to take advantage of the positive attributes associated with oligo-based array CGH.
“We switched to oligo arrays because of better manufacturing quality assurance, greater resolution of genomic regions, and belief that oligo platforms will prove to have multiple advantages going forward,” Beaudet wrote.
According Beaudet, Baylor has initiated two partnerships to enhance its CMA service. The chips will now be manufactured by Agilent, while Athena Diagnostics, a Worcester, Mass.-based international testing service, will handle the marketing and sales logistics for BCM.
Under the collaboration with Athena, set to take effect next week, BCM will continue to perform all laboratory testing, review results, and final interpretations, while Athena will market, sell, acquire samples, issue reports, and bill customers, according to Beaudet.
However, the deal excludes Baylor’s prenatal diagnostic service, which Baylor will continue to administer as it has since it was launched in fall 2005.
A notice sent out by BCM explaining the Athena deal cited Athena's "extensive experience in justifying insurance payment for genetic laboratory testing" and said that the agreement is intended to "improve accessibility and streamline reporting and reimbursement processes."
The Agilent Chip
The same notice also heralded BCM's decision to be the "first to introduce oligo-based array CGH into routine clinical use in North America."
Up until that decision, BCM was like its rivals Signature Genomic Labs, CombiMatrix Molecular Diagnostics, and Empire Genomics in that it offered its analysis using a BAC platform rather than oligos. Oligo-based CGH platforms are sold in North America for research purposes by companies like Agilent and NimbleGen Systems, while UK-based Oxford Gene Technology has been developing an oligo-based diagnostics platform for use in European cytogenetics labs.
According to the notice, which Beaudet provided to BioArray News, the new Agilent-manufactured platform will have essentially the same coverage as the current BCM version 6.1 BAC array. The oligo array contains multiple oligos for each of the BACs on the version 6.1 array, which contains more than 1,475 genomic clones, according to Baylor's website.
"The new array has 44,000 oligonucleotides of 60 base pairs. This means an average of about 28 oligos per region previously covered by a single BAC clone. Because each oligo is carefully selected and is free of any repetitive sequence, the signal-to-noise [ratio] for oligo arrays is intrinsically superior to BAC arrays," the notice states.
Baylor believes that transitioning to oligo arrays will "improve the quality assurance for production of arrays and will offer the possibility of easier upgrades in the content of future arrays as clinical implementation continues to advance to higher resolution genome analysis," according to the notice.
Furthermore, all abnormal results will continue to be confirmed by fluorescent in situ hybridization and partial karyotype, and all results will state whether the sample has been analyzed using a BAC, oligo array, or both, the notice states.
According to Agilent, the deal with Baylor is solely for manufacturing and does not reflect a wider interest in the diagnostics space. In the past, the company has openly discussed the option to use its arrays in diagnostic assays, such as leukemia testing (see BAN 4/4/2006).
Agilent spokesperson Frank Orrico told BioArray News in an e-mail this week that Agilent's relationship with Baylor is one of a vendor to a customer. "Agilent’s role is strictly to print Baylor's content onto glass slides," Orrico wrote. "Baylor is responsible for the final test. Agilent markets genomic microarrays for research use only and will continue to do so for the near future."
Orrico wrote that, despite the deal with Baylor, Agilent cannot "speculate on the extent of use of our microarray platform for diagnostic applications now or in the future. We market the microarrays for research use only, but we can’t know how they’re all being ultimately used."
The Debate Resumes
In the past, Baylor had found itself at the center of a debate over its decision to offer array CGH prenatal testing at a time when other services in the arena, such as Signature Genomic Labs and CMDX, said that the technology was too new to be used to counsel expectant mothers about risks associated with their pregnancies. However, the recent decisions by Signature and CMDX to also initiate prenatal screening have softened that debate (see related story, this issue).
Agilent cannot "speculate on the extent of use of our microarray platform for diagnostic applications now or in the future. We market the microarrays for research use only, but we can’t know how they’re all being ultimately used."
Now, by transitioning to an oligo platform, Baylor has once again found itself in the spotlight of the array CGH community. CMDX CEO Mansoor Mohammed, who is aware of Baylor's decision, last week told BioArray News in an e-mail that the use of oligos in CGH testing creates situations where results may not be easily verifiable.
"Array CGH is being incorporated into clinical cytogenetics, a discipline defined by its reliance on visual observation and correlation to that which is easily confirmable by standard means," he wrote. "In BAC-based array CGH, each data point is in essence a FISH probe; a data point that is easily verifiable. This is not the case when oligo arrays are used in CGH applications," he added.
According to Mohammed, the "sheer numbers of oligo probes that must be used to represent the genomic coverage of a comparable BAC array, often minimally 20 to 30 oligos per BAC, necessitates the use of complex algorithms for data noise reductions, normalizations and ratio generation.”
“The latter renders the copy number analysis generated from oligo array CGH experiments one step further removed from routine clinical practice, and creates an undesirable ‘black box’ image for this transformative technology," he wrote. Still, he maintained that oligo-based array CGH will find a place in the routine practice of clinical cytogenetics eventually, but "we and many other leaders in the industry believe that that time has not yet come."
Another industry leader is Lisa Shaffer of Signature Genomic Labs. "I think oligos are a great research tool, but I have concerns about its use in diagnostics," Shaffer told BioArray News in February 2006 (see BAN 2/14/2006).
"There's so much noise associated with oligos that it would be almost impossible for a diagnostics lab to follow up on every oligo that falls outside of your normal range," she said at the time. "I think someday the technology is likely to move in that direction, but I don't see it happening in the next couple years," Shaffer added. Signature uses a BAC array to diagnose chromosomal abnormalities and verifies its results with fluorescent in situ hybridization.
Still, Mohammed and Shaffer's criticisms have not been shared by OGT, which has developed its own oligo-based CGH platform for diagnosis of syndromes and is currently evaluating ways of making it more broadly available in the UK.
In October, OGT CEO Mike Evans told BioArray News that “the noise issue associated with oligonucleotide arrays is becoming far less of an issue as we improve both our aCGH protocols and also optimize our probe design” (see BAN 10/3/2006).
“We are confident that the benefits of enhanced resolution and reproducible manufacture will rapidly result in olignonucleotide arrays replacing BACs as the array of choice,” Evans said. OGT is expected to provide an update on the progress of its syndrome chip later this year.