Rosetta Biosoftware said this week that Almac Diagnostics will use its Rosetta Resolver gene expression-analysis platform to help it develop cancer diagnostics based on Affymetrix microarrays.
The agreement underscores Rosetta's strategy to move its software platform closer to the clinic in step with microarray technology, and follows a diagnostic collaboration with Agendia, the developer of the array-based MammaPrint breast cancer recurrence test, that Rosetta announced in October [BioInform 10-10-05].
Yelena Shevelenko, vice president and general manager of Rosetta, said that the two agreements differ in scope, because the Almac deal is solely a licensing agreement while the Agendia pact also includes a research collaboration. However, she said, both deals "emphasize the versatility of our system — how it can be used for both discovery of biomarkers and development of the platform to bring those biomarkers to the clinic."
Biomarker discovery and diagnostic development are quickly becoming the "prominent focus" for Rosetta, Shevelenko said, noting that the company plans to work with Almac to ensure that its software aligns with Almac's development goals.
"The most exciting part for us is to see now Almac will develop their platform — their arrays in this case — to move biomarkers from discovery to the clinic," Shevelenko said. "That's a very important part for us. We want to understand what the needs are to move utilization of our tools into the clinic in the future."
Rosetta is surely eyeing the potentially lucrative diagnostic testing market — along with its competitors — but the company is in no rush to push its software into the clinic.
A growing number of firms are developing diagnostic tests on microarray platforms, with Almac and Agendia joining a list that includes Osmetech, Combimatrix Molecular Diagnostics, BioMérieux, Veridex, Roche, and others. But even as these firms drive their tests closer and closer to the clinic, there are still open questions regarding the software requirements for validating and supporting array-based diagnostics, according to Vitali Proutski, bioinformatics manager at Almac.
The software used in validating a potential diagnostic "obviously … should be developed according to certain standards," Proutski said, "but it may be necessary that not only the software per se is developed according to certain standards, but that the processes that are used for validation — statistical mechanisms, statistical engines to do certain calculations — are also validated. So that you know every time you put the same data in, you get the same results out."
The problem, he said, is that no commercial software packages currently offer that capability.
There are even bigger questions regarding the software that will eventually support microarray-based tests in the clinic, Proutski said. "What you want is some kind of software that will take a readout from a microarray or other device, and convert it into a clear clinical suggestion. Something that a physician can understand and make a decision — drug X should be given to patient Y or should not be given to patient Y."
This capability, however, "happens to be an incredibly difficult thing to do," he said, "and as far as I know, there are no software systems doing it well at the moment."
Even Roche's AmpliChip — the first microarray-based test to hit the market with FDA approval — is not sold with software that enables physicians to quickly interpret the test's results, Proutski noted, adding that the AmpliChip CYP450 genotyping test is actually "simple" compared to the gene expression-based tests that Almac is developing.
"What we're talking about is in fact much more complicated because we're not talking about binary answers — is there a polymorphism or isn't there? We're talking about, say, a list of genes — maybe 20, 50, 30, even five of them — and each of these genes will have a certain level of expression, and this level of expression is not going to be absolute. … There will be a level of probability assigned to this gene predicting that such and such drug should be given in combination with similar probability values for other genes," he said.
"So it's going to be sort of fuzzy logic, and you can imagine that reading this kind of information from the device will simply say nothing to a physician."
Proutski said that Almac scientists are currently "debating" these issues. In the meantime, he said, the company opted to move its analysis efforts from Agilent's GeneSpring software to Rosetta Resolver because the company needed a system with better data-management capabilities and the ability to support CFR 21 Part 11 compliance.
Almac considered other systems, including Genedata's Expressionist and Stratagene's ArrayAssist, but Proutski said that Resolver's data-management features made it "the best buy" even though it was the most expensive out of all the systems it evaluated.
Proutski cited the Resolver's flexibility as another positive feature — particularly the fact that it is integrated with the R statistical programming language, which enables the Almac team to add Bioconductor modules or its own scripts.
Almac will also use Resolver in its genomics services offering, which uses Affymetrix GeneChips.
Going forward, Proutski said that Almac has two options for developing the software that will accompany its chips to the clinic: it can either develop the software internally, "or try to do it in partnership with another company interested to go all the way with us, and maybe even share the risks."
Proutski said that Almac is considering Rosetta as a potential partner for this stage of its development plans, but stressed that "no decisions have been made about whether it will be Rosetta or somebody else."
Rosetta is surely eyeing the potentially lucrative diagnostic testing market — along with its competitors — but Shevelenko said that the company is in no rush to push its software into the clinic. "I think we are still trying to understand what the requirements will be and what kind of changes we will need to make [to the software]," she said. "We will play a role there, but we don't have a clear picture to comment on at this point."
— Bernadette Toner ([email protected])