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Genetic 'roadmap' charts links between drugs and human disease

am to compare the signatures of the drugs with each other and also with the signatures seen in diseases. Using the Connectivity Map, the scientists were able to discover the mechanisms underlying a novel drug candidate for prostate cancer, and that a drug currently used to treat one disease may be useful in another.

"This is a powerful discovery tool for the scientific community," said Justin Lamb, the lead author of the Science paper and a senior scientist in the Broad Institute's Cancer program. "By analyzing just a small fraction of available drugs, we have already confirmed several biological connections between drugs and human disease, and made entirely new ones, too."

Like other scientific databases, the true value of the Connectivity Map lies in its capacity to be queried by nearly any researcher with a computer. The genomic signature of a particular human disease, drug or other biological response of interest serves as the search "word" and potential functional connections are revealed through a rank-ordered list of reference compounds in the database that have matching signatures.

One of the surprising results to emerge from the Connectivity Map involves gedunin, a plant derivative that, despite a long history of medicinal use, is not well understood molecularly. The researchers identified gedunin in a high-throughput chemical screen for molecules that disrupt hormone signals in prostate cancer cells and then used the Connectivity Map to help uncover its precise molecular action. As confirmed through additional work, gedunin disrupts a key quality control mechanism in the cell.

Another key finding suggests a new way to overcome drug resistance in cancer. Using the Connectivity Map, a scientific team led by Scott Armstrong, an assistant professor at Harvard Medical School and Children's Hospital Boston and an investigator at the Dana-Farber Cancer Institute, identified the FDA-approved immunosuppressant drug, sirolimus (al
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Source:Broad Institute of MIT and Harvard


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