MicroArrays Take on Signal Tranduction

Researchers at Rosetta Inpharmatics Inc. (Kirkland, WA) have combined DNA microarray technology with bioinformatics in a novel way to track signal transduction pathways in yeast. Described in the February 4 issue of Science, this approach confirmed information already known about these well-studied pathways, and identified novel connections, which were themselves confirmed through independent experiments.

The group, which included Canadian scientists from Queen's University (Kingston, ON) and Samuel Lunenfeld Research Institute (Toronto), used genome-wide transcript profiling to monitor the mitogen-activated protein kinase (MAPK) cascades underlying pheromone signaling, cell cycle control, and polarized morphogenesis. Hundreds of genes were found to be either up- or down-regulated in response to pheromone treatment. From over 40 different experimental conditions, a two-dimensional matrix was constructed, which identified conditions that led to similar global patterns in gene expression. Also revealed by this analysis were internal feedback loops and higher order signaling pathways.

Access to the data generated by these experiments will be provided to academic researchers upon request.

"This is a major advance in the field of genomics because until now it has been assumed that, to study all proteins in the cell simultaneously, one has to use proteomic approaches such as mass spectrometry. We've shown that much can be learned about protein activities simply by looking at the expression patterns of all genes in the organism," stated Stephen Friend, senior author of the paper and president and chief scientific officer at Rosetta.

A critical feature in this analysis, according to Rolan Stoughton, vice president of bioinformatics at Rosetta, is the ability to efficiently mine and interpret the massive amount of data generated in gene expression experiments. The company's Resolver data analysis system will enable them to capitalize on subtle changes in gene expression to reveal potentially important targets easily missed by other approaches.

Resolver System Plot Viewer

Rosetta Inpharmatics, founded in 1997 by Friend, Leland Hartwell, and Leroy Hood is dedicated to developing DNA microarray expression information. The company's integrated platform comprises FlexJet DNA Microarray technology, a flexible "next generation" DNA microarray platform employing proprietary modifications of a standard ink-jet printing process; the Resolver Expression Data Analysis System; and advanced molecular biology techniques, which permit the exploration of the diverse causes and consequences of changes in gene expression. These tools allow researchers to focus on those cellular processes that are specifically affected by disease or exposure to pharmaceuticals, chemicals, environmental conditions, or genetic engineering.

The Resolver system is distributed through Rosetta's strategic partner, Agilent Technologies (a subsidiary of the Hewlett-Packard). Rosetta supports the expression profiling programs of pharmaceutical, biotechnology, agrochemical, and ag-biotech companies worldwide. Access to FlexJet DNA Microarray technology is available from Rosetta Inpharmatics only through a collaboration.

For more information: Stephen H. Friend, Rosetta Inpharmatics Inc., 12040 115th Ave. NE, Kirkland, WA 98034. Email: sfriend@rii.com.

By Laura DeFrancesco