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Facing Increased Competition in CGH Testing Market, Signature Debuts New Chips, Service

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Signature Genomic Laboratories, a Spokane, Wash.-based service firm that specializes in using array comparative genomic hybridization to diagnose genetic abnormalities, will retool its offering this month by launching two diagnostic chips and a service it hopes will lure cytogenetic labs that are put off by the idea of outsourcing tests.
 
Lisa Shaffer, Signature’s president, co-founder, and CEO told BioArray News that the company plans to release two next-generation arrays next month that will replace its SignatureChip platform: One, like the SignatureChip, will be based on bacterial artificial chromosomes; the other, an oligonucleotide array manufactured by Agilent Technologies, will mark the company’s first oligo-based product.
 
The development of an oligo-based array for CGH-based diagnosis represents a shift in strategy for Signature, which had previously considered oligo chips to be too noisy for use in routine clinical diagnostics. Shaffer said the decision was based on Signature’s faith in its internally designed array, which the firm believes may be more useful for some customers than oligo arrays from other vendors. In addition, she said, the move was a response to pressure from an increasingly competitive marketplace.
 
“Our clients want higher resolution. They have been hearing about oligo chips from competitors and they think they are better, and in some cases they are better, depending what they are looking for,” Shaffer told BioArray News last week. “That’s why I think that … providing this option will give us a real advantage.”
 
Signature’s two new chips are called the SignatureChip Whole Genome, which is composed of BACs, and the SignatureChip Oligo Solution, which is essentially the SignatureChip WG manufactured with oligonucleotides. According to marketing material provided by Signature, the company views each as having its own advantages and disadvantages for particular customers.
 
The SignatureChip WG contains more than 4,700 BAC clones with coverage of more than 150 chromosomal syndromes and contigs of clones in every band at 850-band resolution. It is unlikely to detect alterations with unclear clinical significance, an attribute that Signature believes will aid in making a higher-confidence diagnosis for its clients, but may make its sister array more attractive for certain cases.
 
SignatureChip OS, on the other hand, contains 105,000 features per array with an average of 50 oligos per clinical target and the same syndrome coverage of the SignatureChip WG. The array also has a backbone of one oligo for every 35kb. Its strength, according to the company, is its ability to detect gene alterations that cannot be detected using BACs. However, a potential disadvantage is that it may be impossible to confirm such a finding using fluorescence in situ hybridization, the firm said.
 
Shaffer said the company will launch SignatureChip WG on Nov. 1, while Signature OS is currently being validated and is expected to debut a month later. Signature will continue to offer the Signature MarkerChip, which offers analysis of pericentromeric regions to identify the chromosomal origin and further characterize the extent of imbalance of marker chromosomes, as well as its PrenatalChip, designed specifically for prenatal diagnosis, without any changes.
 
With SignatureChip WG, “we targeted all the pathways that we feel are critical for [human] development,” Shaffer said. “In doing so we ended up with little over 4,700 clones. We FISH-verified every single clone,” which was “worth the effort because this is a huge resource for our clients.”
 
For the SignatureChip OS, the company used the WG as a template, Shaffer said. “The reason we will be able to introduce this chip is that WG was built properly and secondly now we have FISH probes that correspond to all the loci in our FISH library” which helps confirm a diagnosis, she added.
 
Oligos vs. BACs Redux
 
Signature’s move to offering an oligo-based chip echoes a similar decision in April by Baylor College of Medicine’s Medical Genetics Lab to offer an Agilent-manufactured oligo array for all diagnoses outside of prenatal (see BAN 4/3/2007).
 
Other firms in the marketplace, like BlueGnome, Empire Genomics, and CombiMatrix Molecular Diagnostics, continue to sell BAC arrays. In September, Graham Snudden, Blue Gnome’s vice president of engineering, said that his firm could technically offer an oligo-based version of its CytoChip, but that a BAC platform is “what serves the patient group most” (see BAN 9/11/2007).
 
Others entering the market do not agree. For instance, Oxford Gene Technology’s R&D Director John Anson told BioArray News in June that “oligos offer greater probe density and greater security and confidence in the data” and are more amenable to the large-scale manufacturing necessary for routine diagnostic use (see BAN 6/26/2007). 
 
For Signature, though, the solution to the BACs versus oligos debate is to simply offer both. “We firmly believe in a BAC-based chip and we have felt enormous pressure from the market to introduce an oligo chip,” she said.
 

“We firmly believe in a BAC-based chip and we have felt enormous pressure from the market to introduce an oligo chip.”

“We are the only lab now that offers a choice. The main advantage of OS is that you can detect very small alterations like the size of a gene,” she said. “Some deletions are very small; you have the potential of missing them if just [one] gene is deleted. So the OS will detect that. Depending on the symptoms, you might want to be identified with the OS.”
 
In terms of the manufacturing issue, Shaffer said it costs Signature more to manufacture oligo chips through Agilent than to make BAC arrays in house. Nevertheless, the company decided to keep the cost of the WG and OS services the same, at $1,650, because it doesn’t “want the cost to drive the decision making. If someone needs the oligo array, then I don’t want finances to be a barrier to them.” Shaffer said.
 
Genoglyphix
 
Signature has also introduced another new offering to retain its presence in the CGH-testing services market. The service, called Genoglyphix, allows cytogeneticists to analyze and interpret test results generated using Signature’s array technology.
 
Under Genoglyphix, customers can choose from two service plans: a technical-only option, where they can view test results online and sign out cases processed at Signature’s laboratory; or they can purchase Signature’s SignatureSelect research-use-only microarrays for in-house use. Both plans give users access to Signature’s in-house software to visualize the test results, browse the genome databases, and order BAC clones used on the firm’s chips for FISH testing.
 
The company expects the SignatureSelect arrays to interest institutions that have their own cytogenetic labs. “They would prefer to do analysis themselves rather than to send out samples to a reference lab,” Shaffer said.
 
”The issue for these labs is actually reimbursement, said Shaffer. “They want to do the test themselves so they can manage their cost level.”
 
The “technical-only” offering is similar to CMDX’s “tech only’” service. In CMDX’s case, the firm receives samples from clients, runs the tests, and provides clinicians with data for their own interpretation. According to Shaffer, “technical only” has been available through Genoglyphix since March, while the SignatureSelect arrays were released this fall.
 
In the past, Signature had appeared hesitant about selling its chips to other labs, due to the threat of end-user error. In October 2005, Shaffer told BioArray News, "I don't want to be the one that's dealing with a customer that says 'your chip doesn't work' and having to tell them, 'well it works; you're just not doing it right.' I don't want to have to troubleshoot 300 labs in the country." (see BAN 11/2/2005).
 
Signature has now reversed its position to meet demands from its clients, Shaffer explained last week. “We realized that some of our clients were going to leave us because institutions were saying they wanted to bring [the testing] into their own cytolabs and we would like to keep them in the Signature family,” she said. “So yes, we have changed our attitude.”
 
Exponential Curves
 
But what kind of market forces pressured Signature into making such chips and services available? Shaffer pointed out that over the four years since the firm was founded, it has grown from three to 52 employees and done 14,000 cases. Beyond that growth, though, has been a parallel increase in the number of labs offering similar services.
 
“We were the first to enter this field and we are now experiencing competition,” she said. “There are now a number of labs, universities, and companies who are also offering testing,” she added. “We have always been on this exponential curve but lately it’s flattened off a bit because of competition. I would imagine that nationwide adoption of array CGH is on an exponential curve,” Shaffer said.
 
“There has been wider acceptance in the field by not only geneticists but other practitioners such as neurologists and pediatricians. All disciplines of medicine that would typically send a sample in for a karyotype are becoming comfortable with this technology,” said Shaffer.
 
“We are also publishing a lot and probably the medical literature is the best reference point for clinicians,” she said. “I think it’s because of word of mouth and the literature that people are becoming aware of this technology.”

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