Google-like search tool links disease-related genes to possible drug treatments.

Scientists have begun connecting the dots between genes and diseases, but translating what they are learning into effective treatments has been difficult. Now, HHMI investigator Todd R. Golub and his colleagues have created what they dub a "connectivity map" to link diseases, genes, and small drug molecules.

"The problem is that the language typically used to describe diseases is based on signs and symptoms from the patient and on what disease cells look like under the microscope," says Golub, who is based at the Broad Institute of the Massachusetts Institute of Technology and Harvard University. "Small molecules and drugs are described in a totally different language—the language of chemistry."

To dissolve that barrier, Golub's team has effectively created a computerized search engine—not unlike Google, says Golub. The "user," or investigator, first compiles a list of genes that are known to be important in the disease being studied. That list is used to query a database of drug-responsive genes, or genes that were turned on or off in cell lines that were individually treated with various drugs. The goal is to find a "hit," or gene match, between the disease genes and the drug-responsive genes.

In their work, described in the September 29, 2006, issue of Science, Golub's team confirmed known connections and found new ones, including possible drugs for prostate cancer and a particular form of childhood leukemia.

The map is far from complete, however. Only 164 drugs and biologicals were used in this study to represent a broad range of available drugs and compounds. They hope to soon add every drug that is approved for marketing by the U.S. Food and Drug Administration. In the long run, they hope to expand the database to include information from all the inhibitory RNAs that target each of the approximately 20,000 to 25,000 genes in the human genome.

Photo: Photo Researchers, Inc.