PALO ALTO, Calif.--If the attention paid to Molecular Applications Group at a recent gene expression analysis conference is any indication, the company will have little trouble marketing its newest product to the approximately 30 pharmaceutical companies that are customers of Affymetrix's gene chips. "There were a ton of people coming to the booth and wanting to hear about what we were doing," said Nicole Ellis, product manager for Molecular Applications' new Stingray Expression Analysis System. "People are really excited about having tools made to help them with gene expression analysis," she added.
Molecular Applications' gene expression analysis system, being launched this week, is the first fruit of the company's partnership with Affymetrix that began in September. The Stingray system is designed to enable users of Affymetrix's human and mouse array chips to perform sophisticated data analysis. It includes software for clustering genes, graphing gene expression profiles, viewing overlaps between clusters, and classifying pathways. In addition, Molecular Applications' scientists have created a series of databases to support the package--repositiories of mouse and human pathway classification information and annotation data for the 6,000-plus genes on each of Affymetrix's HuGeneFL and MU6500 chips.
Michael Campbell, a senior scientist at Molecular Applications, said Stingray's clustering component lets users quickly and accurately find genes with similar expression patterns across a series of experiments. Manual gene expression pattern detection is error-prone and can take weeks or months, said Campbell, who performed such tasks himself as a gene expression researcher at Stanford University. With Stingray, he said, "one clustering run is done in about 10 seconds. You can set up a series of parameters, hit a button, wait about five to 10 seconds, and then change parameters to generate more, and do it a couple times in a minute."
For example, Campbell said, "Let's say you had 20 or a dozen different samples and you had hybridized your samples to one of the gene chips. What you could do is find all the genes that had a certain expression pattern--such as high in the brain, low in the liver, low in the spleen, maybe medium in the stomach, and very high in the spinal cord--and that would be an example of one expression pattern. He continued, "You could imagine that there could be many different expression patterns across a dozen samples, so the clustering tool is more accurate than doing that by hand, and much faster."
Pharmaceutical scientists with customized methods for clustering can still use Stingray for analysis by importing results of their own clustering output into the Stingray system. Explained Ellis, "We tried to address both sophisticated users who have been doing gene expression for a long time as well as green users."
Campbell told BioInform the pathway databases were created using "a variety of methods including sequence comparison methods, looking at the internet, and doing a lot of hand-curation for putting genes in particular functional categories," such as inflammation. He compared Molecular Applications' classification scheme for the mouse and human pathways to those on a public yeast pathway database curated by the Munich Information Center for Protein Sequences (http://www.mips.biochem.mpg.de/proj/yeast/catalogues/ funcat/index.html). "Generally, these represent the cellular roles of a gene rather than their biochemical function," Campbell explained, adding, "We feel this is more valuable for gene expression analysis because genes in a common pathway are more often coregulated than genes having a common biochemical activity."
Campbell said Stingray employs binomial distribution to identify correlations between types of classifications. "When a user is in Stingray, typically they will find genes that have a similar gene expresison pattern using clustering," he explained. "A biologist will take a number of samples from an experiment--maybe a series of doses of a drug, maybe a time course, maybe different tissue types--then basically extract the RNA, label it up from each individual sample, and then hybridize it to a particular Affymetrix gene chip," he continued.
In a typical gene expression experiment, Campbell said 20 different expression patterns may be found. The binomial distribution function calculates overlaps between those 20 patterns and the 150 different biological categories in the Stingray pathway databases and displays results with a matrix viewer, Cambell said, adding, "The main thing we've done is make it really easy to get access to the information. The calculations are run automatically once you click on a particular button."
Molecular Applications has exclusive marketing rights for the Stingray databases, and intends initially to target the 30 pharmaceutical companies among Affymetrix's approximately 80 gene chip customers, Ellis said. Molecular Applications will also offer custom databases, but not the software contained in Stingray, to users of array technology other than Affymetrix's. Stingray will be priced either through concurrent licensing or per seat, Ellis said.